Category: Metabolism

Introduction

Recent campaign all over the world in the media geared towards reducing the rates of obesity have with no doubt led to fats phobia and subsequently many people have stopped consuming meals rich in fats. The ironical twist of it all is that fats are a source of energy which is the engine of the body.Adispose tissue famously dubbed fat has the sole role of storing ingested energy in the body (Badman & Flier, 2007).

Fats regulation

A gross rise in the increase of weight has led to serious scientific research and debates to come up with the most efficient way to regulate the human body weight. its worth noting that the main cause of increase in obesity in recent years is as a result of numerous factors but surprisingly and mistakenly all efforts of dedicated towards reduction in consuming meals with fat contents (Badman & Flier, 2007).

Scientific research has been gathered which shows that genetic variations and environmental influences form part of fats related health issues. Studied research shows that a gene known as FTO is responsibly linked to obesity after scanning forty thousand genome wide scans. Carriers of FTO in the cases aforementioned are said to have three kilograms heavier than other people (Badman & Flier, 2007). Basically genes alone cant bring about obesity but their interaction with environment facilitates obesity. The said environment catalyses the process

The likes and the dislikes

Bearing in mind that there other methods of reducing fats in the body, I feel much persuaded to point out that the key role of the brain in the entire fat regulatory process should at all times be put into consideration. Seeing a therapist when stressed and having enough sleep to maintain the right state of the mind while providing an environment for the effective control of the regulatory system by the brain. I like the method of reducing obesity based on the patient instructions of how to avoid certain diets, encouraging them to start physical exercises and to have minimal consumption of food. This helps the patient in the most natural way. Bariatric surgery is another method which entails removing the fatty part of the stomach to minimize the stomach. I dont like this method since it has grievous side effects just like any other surgery. One can die during the surgery and further its not economic friendly (Powell, 2007).

Suggestions

I would suggest that unless effective drugs are discovered without gross effects, people should be advised to utilize the natural methods which are not only easy to adopt.Methods such as giving the brain favorable environment to regulate the amount of the fats in the body are highly recommended. A drug for obesity has been said that it should act through separate ways but to achieve one end (Powell, 2007).

Conclusion

In our tireless efforts to research on the drug and different ways to deal with the excess fats in the body its worth remembering the function of the brain in the regulatory process of fats in the body. Those suffering from obesity should be encouraged to try physical exercises first.

References

Badman M. K. and Flier, J. S. (2007). The Adipocyte as an Active Participant in Energy Balance and Metabolism. Gastroenterology, 132,(6), p. 21032115.

Powell, K (2007). The Two Faces of Fat. Nature, 447, p. 525527.

Hypophosphatemia is a metabolic derangement characterized by an abnormally low phosphate level in the blood serum. Rickets in children occurs due to low phosphate serum levels, while Osteomalacia is due to phosphorus deficit in adults ¹. Osteoporosis may be brought on by an imbalance in the bodys phosphorus and calcium levels in bone metabolism. If the body does not have enough calcium in the blood, metabolic derangement called hypocalcemia develops. Over time, cataracts, dental changes, and other abnormalities may develop due to hypocalcemia. Nails become brittle, hair grows slowly, and the skin becomes delicate and thin due to a lack of calcium. Muscle cramping, mental disorientation, and numb lips and hands are hypocalcemias severe symptoms. Calcium and phosphate ions release promote bone repair by controlling osteoblast and osteoclast activation. The calcium in the serum is affected by the phosphate level. There is an inverse relationship between calcium and phosphate in the body, meaning that phosphate levels decrease as calcium levels in the serum increase. PTH regulates calcium and phosphorus concentrations in the serum. Therefore, calcium and phosphorus interact to affect bone metabolism in the body.

Low blood calcium causes the release of PTH from the parathyroid gland (step 1).

PTH leads to the release of calcium from bones (step 2), leading to an increase in the serum calcium level (step 6a).

PTH affects the kidney by increasing the kidneys conversion of 25-dihydroxy cholecalciferol to calcitriol (step 3). Calcitriol enhances calcium absorption in the brush borders of the intestine (step 6c), increasing serum calcium levels.

PTH acts on the kidney (step 4) to reduce calcium loss in urine by increasing its reabsorption, leading to increased serum calcium levels (step 6b).

Bibliography

Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. 14th ed. Elsevier  Health Science; 2020.

Shaker JL, Deftos L. Calcium and Phosphate Homeostasis. PubMed. Published 2000. Web.

Introduction

Metabolic syndrome is a cluster of biochemical and physiological abnormalities that occur together, increasing the risk of type 2 diabetes mellitus, stroke and cardiovascular disease (Swarup et. al., 2019). There is growing interest surrounding metabolic syndrome due to the current obesity crisis; it is estimated that as much as 1/3 of the US has metabolic syndrome, both diagnosed and undiagnosed (Saklayen et. al., 2018). Sleep is often overlooked but there is emerging evidence that sleep has a key role as a modulator of metabolic homeostasis (Koren et. al., 2016). Due to modern society’s busy lifestyles, sleep deprivation has become increasingly more commonplace and research supports that it increases the chances of obesity, diabetes and hypertension (Nagai et. al., 2010). This essay explores the relationship between sleep deprivation and the metabolic syndrome, with obstructive sleep apnoea and the consequences of night shift-work as examples of sleep dysfunction.

Metabolic Syndrome

To be diagnosed with metabolic syndrome patients must have at least three of the following symptoms; elevated waist circumference, high triglyceride levels, low HDL cholesterol, hypertension and high fasting glucose levels (Amihăesei IC et. al., 2014). There is an increasing spotlight on metabolic syndrome due to the global increase in obesity levels, which is an important component of metabolic syndrome. This obesity epidemic has put a strain on our health services; between 2014 and 2015 it was estimated that the NHS spent £6.1 billion on obesity related health issues alone (Gov.uk, 2017). Although there are many other factors responsible for this surge in the occurrence of obesity and metabolic syndrome – such as the marketing of junk food, bigger portions and a more sedentary lifestyle – sleep deprivation is thought to have played a key role.

Other underlying risk factors of metabolic syndrome include ageing, non-alcoholic fatty liver disease and hormonal imbalance such as PCOS.

Sleep Deprivation

It is estimated that most adults require approximately 8 hours of sleep per day (NHS, 2019). However, sleep deprivation is increasingly becoming a bigger problem for society, with 30% of adults reporting to sleep less than 6 hours per night, according to a study conducted by Sharma et. al. Sleep deprivation can be chronic or acute and may range extensively in severity (Medic et. al., 2017). As well as causing fatigue and having a negative impact on mental wellbeing, there is growing evidence to support that sleep deprivation may be a risk factor for metabolic syndrome (Koren et. al., 2016). Conversely, greater than 10 hours of sleep per day was also found to be associated with symptoms relating to metabolic syndrome (Kim et. al., 2018).

Sleep has been found to be essential in maintaining metabolic homeostasis. There are three main pathways that could mediate an adverse effect of sleep loss on the risks associated with metabolic syndrome; changes in hormonal secretion, sympathetic stimulation or inflammation (Sharma et. al., 2010). The focus of this essay is on hormonal changes following sleep deprivation and its association with dysfunction in the HPA axis, leading to neuroendocrine dysregulation.

The Influence of Sleep Deprivation on the Endocrine System

When there is a disruption or lack of sleep, this can cause a dysregulation of the hormones that are involved in managing metabolism (Sharma et. al., 2010).

The pituitary gland releases adrenocorticotropic hormone (ACTH) which acts on the adrenal gland to release cortisol. Cortisol has glucocorticoid effects; it is involved in increasing blood glucose levels and regulating metabolism. This system is illustrated by figure 1. The concentration of cortisol varies throughout the day, with its highest concentrations occurring in the morning and rapidly decreases in the evening before bed. However, a study carried out by Cauter et. al. showed that this decrease in cortisol levels in the evening was 6-fold slower in subjects who had been sleep deprived for 6 days prior. It is therefore thought that the higher levels of cortisol in sleep deprived patients is likely to promote the development of insulin resistance, due to cortisol raising blood glucose levels. Insulin resistance is a risk factor for diabetes and metabolic syndrome, and may help to explain why sleep deprived subjects are more susceptible to obesity.

Other hormones affected by sleep deprivation include growth hormone (GH). Figure 2 shows that the hypothalamus releases gonadotropin releasing hormone (GNRH), which stimulates the pituitary gland to produce GH. GH enhances triglyceride breakdown and oxidation of adipocytes. It plays a critical role in regulating metabolism and also increases insulin secretion and glucose uptake. Studies have found that there are lower levels of GH in sleep deprived patients (Leproult et. al., 2009). GH deficiency is characterised by increased insulin resistance. This is a risk factor for type 2 diabetes, a condition closely associated with metabolic syndrome.

It has also been found that the hormones leptin and ghrelin have a relationship with sleep deprivation and metabolism. Leptin is a hormone that inhibits hunger, whereas ghrelin is a hormone that stimulates appetite. Reduced leptin and increased ghrelin appear to correspond with increases in hunger when subjects have been deprived of sleep (Cauter et. al., 2015).

Sleep Apnoea and Metabolism

Sleep consists of two different stages – NREM AND REM – that occur alternately in 90-minute cycles throughout the night. Metabolism is at its slowest rate during NREM and highest during REM (Sharma et. al., 2010). Obstructive sleep apnoea (OSA) is an example of a common condition that disturbs sleep architecture. During sleep, when the throat and tongue muscles are more relaxed, this soft tissue can cause the airway to become blocked and leads to breathing stopping and starting (Spicuzza et. al., 2015). Syndrome Z is the term used to describe the co-occurrence of OSA and metabolic syndrome (Castaneda et. al., 2018).

There is accumulating evidence to support the importance of effectively diagnosing and treating obstructive sleep apnoea as more is discovered about its long-term effects (Montesi et. al., 2012). OSA causes intermittent hypoxemia due to airway collapse. The subsequent nocturnal desaturation followed by reoxygenation can cause inflammation which damages the blood vessels and leads to hypertension (Dewan et. al., 2015).

Treatment for OSA may include using a CPAP machine which gently pumps oxygen into a mask that the patient wears over their mouth while they sleep. This can improve the patient’s breathing by stopping airways from becoming too constricted, improving quality of sleep and reducing the risk of problems linked to OSA (Spicuzza et. al., 2015).

Night Shift Work and Metabolism

Getting an insufficient amount of sleep is becoming increasingly more typical due to modern lifestyles. For example, night shift work has become highly prevalent in industrialised society and is associated with lack of sleep because of interference with the circadian rhythm (Åkerstedt et. al., 2010). Night-shift work affect mental health and has negative social implications, but there is also growing evidence to support that night-shift work increases the risk of developing metabolic syndrome (Pietroiusti et. al., 2009).

It was found that obesity, high triglycerides and low concentration of HDL cholesterol seem to occur together more frequently in night shift workers than in day workers (Nikpour et. al., 2019). These are all symptoms of metabolic syndrome. There could be many reasons behind these findings, for example the impact of sleep-wake cycles, eating and exercise habits, hormone secretion and blood pressure levels (Brum et. al., 2015).

Disturbance in metabolism of night-shift workers was found to be primarily caused by peripheral oscillators. They detect changes in light and synchronise the body’s organs and tissues. Following a night-shift, 24hr rhythms in metabolites related to the digestive system – which include peripheral oscillators in the gut, pancreas and liver – shifted by 12hrs whereas the biological clock only moved by two. This is likely to have a significant impact on metabolism (James et. al., 2017).

Conclusion

Research strongly indicates that there is a relationship between sleep deprivation and the metabolic syndrome. This is likely due to the fact that sleep deprivation leads to dysregulation of the neuroendocrine system, increased nocturnal sympathetic activity and activation of inflammatory pathways (for example in OSA). Sleep architecture can be disrupted by OSA, which can cause sleep deprivation. OSA increases the chances of hypertension due to damage of the blood vessels caused by hypoxemia as a result of narrowing airways during sleep. Night shift workers have a disrupted circadian rhythm and this strongly associated with increased risk of obesity due to the effects of peripheral oscillators in the digestive organs.

Current methods to treat metabolic syndrome include lifestyle advice and medication to tackle the various symptoms. Weight loss is recommended to prevent OSA and night shift workers are advised to change their schedules where possible to reduce the risk of developing metabolic syndrome. Overall, sleep plays a remarkable role in regulating metabolism and more research should be done on the effects on sleep deprivation to better understand it and potentially minimise the risk of developing metabolic syndrome.

Metabolism is what sustains life, it is the sum of chemical processes happening inside your body to keep you well and functioning at your fullest. From breathing to digestion and even the nervous network which is helping you to coordinate with the outside environment is a part of your metabolism. It is an autonomic process (which means you get to control any part of it) and is controlled by our brain. In short metabolism is the basis for all forms of life on earth. For yourself, metabolism can be depicted in a relative way, like how fast you can burn calories and stay healthier? Metabolism can be a complex term regarding life, exercise and body.

To find about different things which relatively affect your metabolism or metabolic rate, many factors come into play which include:

1. Age. There is an epic fluctuation regarding the metabolic rate in a growing child as compared to an old person. When you are young all your essentials are in their best shape, your body, muscles, bones and all other things are growing. There is an exponential increase in the metabolic rate. But as you get older and weaker, many physiological and hormonal changes start happening and gradually your metabolic rate becomes slower with time.
2. Gender. As though there could be a contradiction regarding this fact, but men are known to have a higher metabolic rate as compared to women.
3. Genetics. Genes play a vital role in maintaining metabolism and other body reactions, changes in metabolic rate can be a result of genetic disorder OR sometimes a hereditary condition.
4. Physical activity. It is a plain truth: “The more you exert, the stronger you get”. Doing exercise is the great initiative, it burns calories faster and help your metabolic rate stay in an optimum range, even when you fall asleep.
5. Body size. Your metabolism is defined by your body weight, a large accumulation of fat than protein delivers the clean message of someone having very slow metabolism and vice versa. Your body and muscular structure defines the metabolic rate upon which you operate.
6. Environmental factors. Any kind of natural change including habitat, climate and atmosphere can change the metabolic rate of a person accordingly. In more colder or warmer conditions your body needs to cope better and that’s why it exerts more. Thus, an increased metabolic rate.
7. Diet. “You are what you eat” – it is a famous saying which finds it application here. Diet is the most prominent factor in determining your metabolic rate and nothing affects it more. If you choose a healthy life style and take in Organic diet, your metabolism is substantially going to get a whole lot faster and better. And the chances with a bad diet aren’t much good.

Your metabolic rate prescribes the rate at which your body burns calories. There are a few tested way by which you can increase your metabolic rate and thus, the fat burning. Of all the energy you get from the food you eat, approximately 60% goes into just keeping you alive by regulating your breathing, heart rate and body temperature. Other 30% finds it use in physical activities like working out, house work and doing other basic tasks. And only 10% is used by your stomach to break the food you eat into compounds which allows your body to work at an optimal rate. Here are some ways by which you can increase the fat burning:

1. Eating healthier foods with a lot of protein, this increases your metabolism and helps the body to burn pre-existing fat.
2. Exerting yourself in Hard physical exercises OR a strenuous work out at gym can lead to enhanced fat burning.
3. Simply by walking and moving more often binds a certain drift to your metabolism and fat burning increases as well.
4. Get a proper sleep! During sleep your body is not taking in food or any kind of energy, so, all these hours your metabolism is still up and running. No matter what you are still burning the extra calories in your sleep.
5. Avoid all type of carbohydrates, especially sugars which necessarily increase fat production and accumulation inside the body. Instead eat organic and aim to stay healthy.

When it comes to diet and certain foods which helps us to achieve a healthy metabolism, nothing can help us more. Food is not only the mean to get energy but also to process it inside our body. The type of food which we eat practically affects our level of metabolism and other changes as well. Here are some healthy foods which can help us to have an optimal metabolic rate:

• A wholesome diet, which is very little processed.
• Protein and fiber related diet, which keeps our Glycemic Index at controlled rates thus, contributing towards a healthy metabolism
• Eating dark chocolate, because it contains more than 70% cacao which has high levels of magnesium. Magnesium helps to stimulate the fat-burning hormone called ‘adiponectin’. Adipose meaning ‘Fat tissues’.
• Considering lean protein which keeps your muscle mass healthy, e.g. lean meats, beans, legumes and other plant related diet.
• Plant based organic food which is minimally processed contain high yield of fibers which contribute to healthy digestion and a more full appetite.
• Good fats which are essential for normal functioning of the body like: almonds, nuts, olive and coconut oil. Omega 3 and 6 which are found abundantly in fish and chia seeds.
• Cinnamon acts as an anti-inflammatory and helps to keep our fat content in check, it also helps to contribute in fight against the fat.
• Using low processed foods especially without sugar can help to increase the metabolic rate and keep a healthy life style.
• Drinking a plenty of water everyday can substantially lead towards a more effective and healthy metabolism, excessive water keeps the fluid level at moderate and helps in detoxification along with burning of fat itself.

Superfoods refer to mostly plant based foods including some fish and dairy contents as well, these foods are thought to be nutritionally dense and are considered good for one’s health as a result of its nutritional analysis. Here is a list of some incredible superfoods which can keep our metabolism healthy:

• Chilies, jalapeño and other hot peppers which contain high levels of capsaicin, which increases the fat burning process. Minute quantities are considered beneficial.
• Whey protein contains high density of protein which increases muscular mass and keeps our metabolic rate at an optimum level.
• Pineapple, apple, grapefruit and citrus fruits are all superfoods which moderates our metabolism.
• Garlic and other leafy vegetables due to their high nutrient density can increase fat loss over time.
• Lentils, beans and legumes are believed to have a right mixture of favorable nutrients which help us to keep our metabolism in check.
• Fish and other dairy products can deliver the optimum states of metabolic rates.

Exercise is as important to lead a healthy life style as eating healthy. By doing exercise on regular basis you exert yourself through strenuous tasks which makes your muscular system more strong and proactive. Your cardiovascular system becomes more efficient and your lungs capacity also increase. You can easily tackle all the daily tasks with improved levels of energy. Also exercising delivers more oxygen and nutrients to the body tissues and help to achieve an even basis for the metabolic rate. Here is some profound importance of exercise:

1. Exercise helps to control weight and burn fat easily.
2. Exercise helps in release of certain neurotransmitters which balances mood and energy as well.
3. Exercise promotes better sleep.
4. Exercising can be fun and social as well.
5. Exercise helps you combat diseases and health conditions.

A contrast shower is referred to as a combination of both hot and cold water used in certain intervals to achieve a unifying health benefit. Whereas the hot water dilates the blood vessel and increase blood circulation, the cold shower do the exact opposite, constructing a perfect rhythm of harmony and balance for the metabolism of the body. Other benefits include: improves circulation; relieves depression; keeps skin and hair healthy; increases energy; gives body a tough and rigid feel; burns fat and bring down calories simultaneously.

As it gathers there are many factors which contribute towards a more rich and risk free life style, some of these better increase our understanding about who we are and where our health practices may lead us. Having a complex lifestyle gathers for more health challenges in the long run. That’s why we should consider using a multi process approach. In order for our metabolism to stay normal and working hassle free, we should consider exercise, movement and sauna practice as our priorities. As many benefits of exercise have already been listed above, let us talk about benefits of using sauna bath:

• Inhaling vented steam from water boilers help our nerves to become dilated which increases blood flow and improves cardiovascular function.
• It helps to relieve pain from muscles and joints or after a serious injury or strenuous workout.
• The moist heat taken up by our body helps in removal of certain toxins and drugs.
• Sauna bath also help us to relieve the stress and induce a deeper sleep.
• Saunas also burn calories and help us to combat certain diseases as well.

These were some crucial benefits of using sauna bath, as long as movement is concerned, it is the greatest motivation of all. Nothing good comes by if it isn’t for movement. We have to move in all steads of walk and function at our best, only then we are able to cope ourselves better with our environment and surroundings. As long as movement does not stop life goes on.

These days individuals have accepted that for each 1 pound of muscle you gain, your body consumes an extra 50 calories. On paper, this sounds great. But it is not true, sadly. When we speak about metabolism like it’s something, we can control by swallowing a pill, bringing down some green tea, or running quicker. Let’s be evident about one thing: miracle metabolism boosters are not there. Regardless of what you find in promotions or hear in your running circles, there are no exceptional enhancements or super sustenances that can take off to expand your metabolism arbitrarily or cause you to have more muscles.

Definition of Metabolism

Many individuals talk about their metabolism like it’s a muscle or organ that they can flex or some way or another control. They think as though it’s some genie in a container sitting tight for you to locate the magic light. It’s not like that at all. Your metabolism is merely the method of using your body to live with a certain quantity of energy. It reflects the number of calories you’re burning to maintain your heart beating, your neurons firing, and the numerous other tasks you’re doing without thinking to help your body.

The body’s real organs – the cerebrum, liver, kidneys, and heart, represent about a portion of the energy consumed very still, while the remainder is accounted for by fat, digestive system, and particularly the muscles of the body.

The larger you are, the greater your metabolism, because there’s a greater amount of you to continue running. Genetics also plays a part, as some individuals naturally have greater metabolic rates and consume more vitality when sitting. Metabolism likewise normally decreases around one to two percent for every decade with age.

Increased Muscle Mass and Accelerated Metabolism

Does it make you mad when someone somebody discusses changing over fat to muscle? Because as you most likely are aware, muscle and fat, as you understand, are distinct tissues, too.

Perhaps the most significant difference between the two is that muscle is more metabolically dynamic than fat. A few specialists predict that every additional pound of muscle you increase consumes 30-50 additional calories daily, while others estimate that a pound of muscle consumes 6 calories at rest, contrasted with 2 calories consumed by a pound of fat.

Muscle is more metabolically dynamic than fat, and building muscle can help increment your metabolism. This implies you will consume more calories every day, even at rest. Indeed, even the more moderate gauge implies that it’s valuable to your metabolism to be strong.

Strength Training helps construct muscle, which can boost metabolism. Muscle mass has a greater metabolic rate than fat, which implies more energy is needed to maintain muscle mass. An individual’s body normally loses muscle as they age. This impact can be counteracted by regular resistance training. Resistance training can require lifting weights and doing muscle-building exercises using body weight or resistance bands.

Don’t Attempt to Lose Weight by Muscle Gain

When you attempt to get more fit, you should ONLY be centered around getting more fit, nothing else. Many individuals believe their metabolism is accelerated by gaining muscle and allowing them to eat whatever they want.

In reality, to lose 1 pound of fat per week, you would have to earn 100 pounds of lean muscle, and this is difficult to do even with steroids. Primary concern: use muscle to form your body, not burn fat, and reinforce it.

More Muscle Mass, Higher Metabolic Rate

One thing that can boost the metabolic rate of a person is building more muscle mass. While the caloric consumes of a solitary pound of muscle at rest is particularly exaggerated, the work you’d have to do to construct that muscle would at present make positive changes for your body.

According to estimates, every pound of muscle burn at rest about six calories a day, claims Dr. Church. It’s about three times as many calories as a pound of fat, burning about two calories a day.

It’s essential to remember that these estimates are just that since everyone is distinct. How the numbers function will differ for each individual. Such a large number of components like hereditary qualities, hormones, rest, and diet, can change the rate at which our bodies consume calories. Furthermore, a few people may have a harder time than others when it comes losing fat or acquiring muscle, some individuals may have a harder time than others— again, there are so many variables at play, and our body sciences are for the most part extraordinary.

The Bottom Line

Truly, you can support your metabolism, however nothing unexpected here—there is no silver projectile. In spite of what Instagram influencers or tricky ads will persuade, the techniques for boosting your metabolism are similar propensities for a solid and dynamic way of life. While adding more muscle does not accelerate your metabolism as much as you would like, don’t exaggerate the effect on the metabolism of your baseline. Realize instead that there are many excellent reasons for exercising and adding more muscle (and dropping fat) as a way to be healthier and look better.

Metabolism is defined as the summation of all chemical reactions that occur and are involved inside of any cell or organism. Metabolism has two potential categories: catabolism and anabolism. In catabolism, molecules are broken down producing energy. In anabolism, combinations of certain compounds that are needed by the cells are produced including: DNA, RNA, and protein synthesis. The definition of bioenergetics is the metabolic passageways a cell takes to acquire certain energies. Nutrition science studies the specific relationships with food matters and living things.

Metabolism is a compilation of chemical reactions that takes place within a cell. Metabolism primarily deals with the food we eat. It changes the fuel in the food into the necessary energy to command every single action that one does. This can be a wide range of activities from movements such as walking or typing to physiological actions as complex as cardiopulmonary and cardiovascular pumping. The energy that is produced in the metabolic chemical reactions is neither solar nor thermal energy, but rather ATP energy. ATP, also known as Adenine triphosphate, is a nucleotide, which is a monomer of a protein, that can store and transfer energy very diligently either around the cell or intercellular. ATP is the particle that helps us control all of our bodily functions pertaining to the cells in our body, so everything from breathing to digesting is strongly aided by ATP energy. Chemically, ATP is simply a nucleotide of adenine bonded to three phosphates where most of the energy is stored in-between the second and the third phosphate group. The energy that is located between these two groups is attributed as the main factor in most of the chemical reactions throughout the body. The ATP is arguably the most important particle in our cells due to the simple fact of if all ATP production in an organism’s cells, then very soon, that organism would perish since there is no force to keep the cells active (Marie, 2016).

Catabolism is one of the first and most crucial steps in the metabolism process. Catabolism is primarily the arrangements of enzyme-induced reactions from which larger molecules in majority of living cells are broken down or corrupted. Part of the chemical energy released throughout catabolic processes is saved in the form of energy-rich compounds. Energy is only released in three phases. In the first stage, large molecules like proteins, polysaccharides, and lipids are broken down; small amounts of energy are released in the form of thermal energy in these expansions. In the second phase, the small molecules are exposed to copious amounts of oxygen, freeing chemical energy to form ATP as well as heat energy, to form a variety of compounds including: acetate, oxaloacetate, or a-oxoglutarate. These are exposed to carbon dioxide during the third phase, a repeated reaction series called the tricarboxylic acid (Krebs) cycle. Hydrogen particles or electrons from the transitional combinations formed during the cycle are transmitted through a succession of carrier molecules eventually to oxygen, forming water (H20). These procedures are known also as terminal respiration and oxidative phosphorylation (Bubnis, 2018).

Anabolism is the second and arguably most important phase of the metabolism process. Anabolism is the set of metabolic passageways that synthesizes molecules from smaller components. These reactions involve energy, otherwise known as an endergonic procedure. One way of classifying metabolic procedures, whether at the cellular, organ or organism level, is anabolic, which is the opposite and accordingly the split of a macromolecule. Anabolism is fueled by catabolism, where large molecules are broken down into smaller parts and then consumed in cellular respiration. Most anabolic practices are driven by the addition of water to adenosine triphosphate (ATP). Anabolic processes generally lean toward generating organs and tissues. These processes produce development and variation of cells and increase in bulk size, a process that involves production of intricate molecules. Examples of anabolic processes are growth and mineralization of bone and muscle mass. Endocrinologists usually classify hormones as anabolic or catabolic depending on which part of metabolism they fuel. The standard anabolic hormones are the anabolic steroids, which encourage protein synthesis, muscle development, and insulin. The balance between anabolism and catabolism is also regulated by daily patterns, with processes such as glucose metabolism changing to match an animal’s average intervals of action throughout the day (Bubnis, 2018).

While metabolism may have several parts, it can also fluctuate greatly. Metabolism can be both low and high. An organism with a low metabolism has problems breaking down fats and lipids as easily as an organism with a high metabolism. Low metabolism is usually characterized by the fact of catabolism not working fast enough to keep up with the intake of different proteins, lipids, and carbohydrates. Many factors, including age, sex (gender), and body size can affect one’s metabolism. For, example, as one ages, his/her muscle mass depletes, which slows down his or her metabolic rate. Additionally, men generally have less body fat and more muscle mass than women do, so on average, a man burns more calories more quickly than a woman. Also, if one weighs more or has a higher muscle mass, they will burn more calories, even while resting than compared to someone with significantly less body fat or muscle mass. Many people in today’s society believe that those who are heavier are less inclined to have a low metabolism but that is not always the case with every individual in today’s world (Hensrud, 2015).

There are an excessive amount of ways to increase your metabolism rate. One of many ways is to eat a copious amount of protein at every meal. This is because it makes one feel full to prevent overeating. Also it would be very beneficial to drink more cold water than sugary drinks due to the large amounts of calories in them. Working out also benefits in losing calories greatly. Additionally, sitting down too often is fairly bad for one’s health so it would be better to stand. Eating spicy foods can also significantly boost your metabolism due to the large amount of capsaicin found in most peppers and spices. There are numerous other ways to increase the metabolism rate in one’s body as well such as drinking green tea and coffee, getting enough sleep, and using coconut oil in foods to reduce the amount of saturated fats included (West, 2018).

So in summation, metabolism is a very crucial factor in keeping a body system healthy all together. Metabolism is a very long and drawn out process of ingesting and decomposing many different types of foods and beverages. Metabolism has many different components to it such as anabolism and catabolism. Anabolism is a process that makes reactions that ultimately produce the proteins that assist in forming the muscles and many other parts of the body. Catabolism is the process of creating energy through terminal respiration and oxidative phosphorylation that can later be used in processes such as anabolism and cellular respiration. There are those in the world who can have high metabolism and those who will have low metabolism, yet there is a way to change that. Rather, there are many ways to change your metabolism rate such as: a healthy diet that includes a large amount of proteins, excessive workouts, and an all around healthy lifestyle. Without metabolism, most of the world’s organisms would be in chronic danger and that is why it is such an important topic for studies.

Fad Diets: Worse for Health than Being Overweight?

All around the world each day, people fret over the numbers on the scale, the size of their clothes, and whether they went over their daily calorie limits. Everything from carbs, fats, and proteins to strict lists of “okay” foods are limited and closely monitored in hopes of losing weight while religiously following the newest diet promising quick results. Dozens upon dozens of well-known diets all have different reasonings for their supposed rapid and long-lasting success, but many appeal to a common concern: speeding up your metabolism for lasting results to keep off weight. However, with so many fad diets so different from one another claiming to have the same effect down to the human cells, it raises the question: what does impact the metabolic rate? Do fad diets really speed up the metabolism and have the lasting impacts they advertise?

Calorie and Food Restricting Fad Diets

Our weight is always looped back to our metabolism when we feel that we’ve been watching what we’re eating, getting moderate exercise, and still not seeing results. We like to say that our bodies just can’t keep up with using the energy of the controlled portions that we do eat, claiming our metabolism is just so slow. Many people take that even further and blame their slow metabolism on their genetics, inherited from generations before them. Oftentimes, no one really asks their doctor about whether they think a slow metabolism is to blame and just take adjusting their diet into their own hands, gearing towards fad diets promising an immediate boost to help their body burn through food so that they can eat as they please after the diet takes hold. Such diets include things like the “cabbage soup diet”, consisting of one specific food group and mainly—you guessed it—cabbage soup, and the “Master Cleanse”, a diet of only juice made with lemon or lemonade, cayenne pepper, maple syrup, and sometimes tea. Somehow, both of these drastically different diets claim to have similar effects, along with many other diets that sound too good to be true or too terrible to try. What many people looking to take a quick and easy route to weight loss don’t realize is that many of these fad diets have the opposite effect, lack sustainability, or are simply more damaging for your health than being overweight.

Limited calories, eating only particular “approved” foods, liquid cleansing, and fasting are common themes across fad diets promising the quickest, longest-lasting results with only a short period of actual dieting. However, these are often the most dangerous and harmful diets, promoting eating far fewer calories than a person needs to function on a daily basis and starving the body of the well-balanced amount of nutrients it needs. Sadly, this is what people are told boosts metabolism and they simply believe what they’re told, never looking into the misconceptions and myths surrounding how the body burns through glucose. Three especially significant common misconceptions include the idea that dieting is only about watching calories, particular foods significantly increase metabolism, and that fasting diets are a safe way to increase metabolism and “cleanse” (Breeding, 2018). While it is recommended to keep an eye on the number of calories eaten throughout the day, nutrients, vitamins, and minerals also matter since the body struggles to break down too many carbs or proteins and the body needs a balanced diet to properly function and undergo all its functions and processes (Breeding, 2018). While some particular foods have been found to increase metabolism, praised by the fitness gurus of social media and TV (for example, coffee, spicy peppers (chili, cayenne, jalapeno, etc.), green tea, and apple cider vinegar), it’s still not healthy nor nutritionally valuable to eat only certain foods, especially foods that commonly flush the body out, irritate digestive systems, or are simply hard to keep down. The increase that they give the metabolism is so slight and short-lived that it’s not really worth choking down apple cider vinegar or tearing up your gut with chili peppers every day just to try to lose weight the quick and easy way (Breeding, 2018). Lastly, fasting. Fasting follows the same idea, as limiting your body of the nutrients, minerals, and vitamins it needs is only harmful and poorly thought out but also leads your body to do the opposite as fasting intends: it slows your metabolism as your body clings to the stored energy in fat, entering a starvation mode (Brown, 2018). By the time the fasting period is over, the body hasn’t even left the “starvation mode” which oftentimes results in weight gain or simply overeating because of prolonged hunger and binging (Breeding, 2018).

Carbohydrate Limiting Fad Diets

In the past decade, fad diets like Keto, Paleo, and the famous Atkins diet have all been very popular, preaching consuming very low grams of carbohydrates and high protein or fats instead. Many praise the low carb diets, as they are geared to turn metabolism off of burning carbs for fuel and towards proteins or fats, reasoning that high protein diets are better for you than high carb and that if your body is using fats for fuel, it will burn stubborn body fat. Despite the reasonable, sound logic people appeal to, the diets certainly have their own side effects hiding in the shadows.

In 2001, the American Journal of Cardiology published an issue by Dr. Margo A. Denke concerning the effects on the body of diets with very low carb restrictions and a high-protein/high-fat goal. Denke debunked the idea that these diets switch what your body uses for fuel and suggested that the real secret to the weight loss is only dropped water weight and ketones that can’t be reabsorbed pushing sodium and more fluid out of the body (p. 59). With less water in the body, dieters experience rapid weight loss and shrinking stomachs as their bloating decreases and they praise fad diets without a clue that it’s only a temporary initial effect (Denke, 2001, p. 59). The journal article also stated several complications that have appeared in children who followed the Keto diet to try to lessen the effects of epilepsy, with side effects ranging from kidney stones and dehydration to osteoporosis, and even suggested that ketogenic diets change the functioning of the brain and nervous system (Denke, 2001, p. 60). While diets like Paleo and Keto seem to have much more sound reasoning than things like juice and tea cleanses, they have their own dangers and questionable long-term effects on the body. Not only that, but they lack sufficient proof of having a long-term effect on metabolism and consistent, sustainable results from start to finish.

Fad Exercising

Almost every article debunking fad diets or metabolism myths reaches the same conclusion: lose weight and improve your metabolism with a healthy, balanced diet and exercise. However, the question of how much exercise remains. Fad diets often push for restricted diet and extreme exercise or severely restricted calories and minimal exercise (if any) during the dieting or fasting period. Some even push “key moves” to target specific areas of the body to melt away fat, but how successful are these exercises? How often do you really need to hit the gym to boost your metabolism? According to Herman Pontzer, with the Hunter College in New York as an evolutionary anthropologist, it’s not as much as many fad diets incorporate. Pontzer and his colleagues studied the Hadza of Tanzania, a hunter-gatherer population, and found that they used only slightly more calories than those in Western industrialized nations on a daily basis (Burrell, 2019). This questions everything people have come to believe about highly active lifestyles and what it means for metabolism, shaking ideas that extreme physical exercise is necessary to boost metabolism or that it has such a pivotal impact. Instead, resting metabolism was suggested as a possible reason behind the lack of difference in the caloric needs for different activity levels in daily life, which in turn draws the conclusion that resting metabolism impacts weight loss more than using exercise to increase activity levels from day to day.

Conclusions

Many diets, believed to be true and reasonable due to myths about what increases metabolism, only result in weight gain through restriction and deprivation of needed nutrients through fasting, cleansing, or cutting out entire food groups. Even diets well known to have sensible logic and to appeal to those who scoff at diets consisting of cabbage soup or grapefruits have been debunked as fluff and sugar-coating over what’s really just a loss of water weight and decreased bloating. Also, extreme exercise to compensate for extra calories taken in is ineffective, as highly active lifestyles have shown a minimal difference in daily caloric needs. Instead, what would be most beneficial for increasing metabolism and resulting in a healthy lifestyle is simply balanced eating with mindfulness to individual nutritional needs with regular moderate exercise and activity, but with the main focus put on balanced nutritional foods.

Metabolism

Introduction

Metabolism is biochemical system that the body uses to convert food to energy in order to maintain life and can be fully simulated at genome scale. Metabolism is partly genetic and largely outside of one’s control and changing it is always a matter of an ongoing considerable debate.

In biology, metabolism is the only system that can be simulated at genome scale and is the best indicator for the cell’s physiological state and the biggest biological network fully described so far.

Nutrition is key when it comes to metabolism because food help building the body and contributes to the repair of body tissues, and also necessary for its efficient functioning. Some perfect nutrition examples will be carbon, hydrogen, oxygen, nitrogen, sulfur, in addition to protein, carbohydrates, lipids, and vitamins.

Metabolism can be divided into two important categories: First, Catabolism: which releases energy from breaking down things and uses compounds ( usually larger) and break them into smaller compounds, and this process helps into creating energy. Catabolism helps the human body to stay active by providing enough energy and meet the body’s needs from cellular processes to body movements.

Catabolic-specific work is for example breaking down the Polysaccharides into monosaccharides ( Starch into Glucose ) and Nucleic into Nucleotides or proteins into amino acids. The body breaks down the nutrients and releases the energy that get stored in molecules of adenosine triphosphate (ATP) in the body. The energy stored in ATP is the result of the anabolic work. Second, Anabolism: helps the body to maintain all tissue and grow new cells with the use simple chemicals and molecules to manufacture many finished products such as the growth and mineralization of bone and increases in muscle mass.

The anabolic hormones included are the hormone of growth, insulin, and testosterone.

Metabolic systems biology

In metabolic systems biology, the value of modeling cell metabolism is not only explanatory of a biological process but also predictive.

The first examples of metabolic systems biology appeared in 1999 and were focused on modeling, connecting, and simulating several cellular processes. Whole-cell modeling, named the grand challenge of the 21st century, is an active area of research.

The methods to model a metabolic system are plenty, the most common ones according to BioMed research international are steady-state analysis such as ‘ FBA’ and it involves a set of linear equations, while kinetic simulations involve ordinary differential equations (ODEs).

Each variable represents the variation of a metabolite concentration, in a dynamic or steady state, where the concentration depends on the rates of the reactions that produce and consume that metabolite. Kinetic models do not assume steady state and therefore are able to model highly dynamic mechanisms, including allosteric and posttranslational regulation, metabolite concentrations, and thermodynamics. Such ODE-based systems contain a large number of equations (differential or algebraic) and require unique kinetic parameter values.

They are highly effective at predicting the behavior of small systems where sufficient experimental data can be collected for model calibration and parameter estimation, but for large systems, the use of kinetic modeling remains challenging because of the increasing demand for systems-level genome-scale analyses has recently led to the huge use of constraint-based steady-state models and their unsteady-state extensions.

A researcher from BioMed Research international have reviewed and covered 15 years of human metabolic modeling (Angione, 2019 ). The method used was based on the research described above that showed and covered these linked chemical reactions happening inside a cell constantly to keep the cell and body alive. Metabolism is a strong indicator for the cell’s physiological state and is an important element in a number of diseases, including diabetes, neurodegenerative diseases, and cancer. The multiple layers of biological organization called Omics is used to characterize individual fundamental things and study their interactions with each other. The author also mentioned that it has become very important and proven affective for biomedical applications to study metabolisms when researching about diseases and aspects of health. Mapping protein expression onto a generic human model is useful in the reconstruction of tissue models such as brain, adipocytes, breast cancer, heart, kidney, myocytes, and hepatocytes. In 2012, a research effort by Karr. provided the first whole-cell computational model of the life cycle of a small pathogenic bacterium, Mycoplasma genitalium. The model includes metabolism, replication of the genome, and cell division.

Metabolism and health

“The absolute best way for someone to change his or her total metabolic rate is by being more active,” says Janet Walberg Rankin, Ph.D., professor of human nutrition, food and exercise at Virginia Tech. Many time the metabolism is all about luck, where the lucky people are able to burn energy from food at a faster rate and are able to eat more than others and not gain extra weight easily mostly due to their genetics.

Boosting metabolism is very important and mostly considered healthy. Although, there are many ways to do so, such as exercising, where it increases metabolism by increasing and maintaining the muscle mass, which leads to burning more calories than fat.

It is also proven that some foods are more likely to help increasing the metabolism than others. Such as increasing the protein portion every meal does increase metabolism because of the extra calories required to digest and process the nutrients. Protein increases metabolic rate by 15 to 30 percent and more with 20 percent than carbs and fats. Drinking cold water, drinking green tea is also helpful, in addition to getting enough sleep every night which is essential to ensure that these hormones remain balanced and can prevent a person from overeating, and help their metabolism. Losing 10 percent of initial weight and maintaining that weight is difficult because of metabolic adaptations. This amount of weight loss reduced total energy expenditure 6 calories per kilogram of fat-free mass per day for subjects who had never been obese, and 8 calories for obese subjects, According to, highly publicized Rockefeller University study by R. Leibel, M. Rosenbaum, and J. Hirsch in New York.

“Healthy Weight Journal” stated that resting metabolism and non-resting energy expenditure each dropped 3 to 4 calories per kg of fat-free mass per day in both groups. (Fat-free mass averaged between 53 and 64.1 kg for the subject groups, suggesting a drop in daily calorie expenditure of 300 to 500 calories.) For a person normally eating 2,500 calories per day, a 10 percent weight loss would predict an excess of 375 calories, says the report. It also says that when the subjects gained 10 percent above their initial weight, total energy expenditure increased 8 and 9 calories per kg of fat-free mass per day. The thermic effect of feeding increased by I to 2 calories and non-resting energy expenditure increased by about 8 to 9 calories. All subjects, 18 obese and 23 nonobese were studied at their initial weight and after one or more changes in weight maintained for at least 14 days. Smokers did not differ from nonsmokers in any measures. Metabolic changes were even stronger during the weight loss or gain process. This natural regulating system with its ‘fine balance,’ added to increased hunger or dysphoria, may account for the poor long-term results of weight loss programs, say the researchers. However, despite their striking findings, they conclude with the ‘obligatory last paragraph,’ so typical of women’s magazines and the scientific press, urging that efforts to lose weight continues.

Conclusion

Metabolism is nowadays considered diagnostic of the phenotype, and therefore arguably the best indicator of the functional state of a cell. Metabolism can also be used to prioritize genes and assess their function and the role of gene perturbations including knockouts. Without such integrated analysis, a gene may incorrectly be regarded as important only due to its highly variable expression value.

Metabolism is simply some chemical transformations by way of cellular respiration, and anabolism within the cells of every living organism. The reactions of the enzymes allow organisms to grow and maintain their structures, in order for them to respond to their environments and meet their daily needs.

Energy is necessary for every human being and helping metabolism with exercising is almost necessary to maintain a healthy lifestyle and a more active daily life because it is a physical act of low to high intensity that relies principally on the energy generating process involving, or requiring free oxygen to sufficiently meet energy demands during exercise. However, certain medical conditions can mess with the metabolic rate, such as thyroid for example, would make a person burn energy faster but could lead to serious health issues in a long run.

Work Cited

1. Angione, C. (2019). Human Systems Biology and Metabolic Modelling: A Review—From Disease Metabolism to Precision Medicine. BioMed Research International, 1–16. https://doi-org.eznvcc.vccs.edu:2443/10.1155/2019/8304260
2. Alliksaar, M. (2001). Metabolism in A-Life: Reply to Boden. British Journal for the Philosophy of Science, 52(1). https://doi-org.eznvcc.vccs.edu:2443/10.1093/bjps/52.1.131
3. Metabolism slows with weight loss. (1995). Healthy Weight Journal, 9(3), 45. Retrieved from https://search-ebscohost-com.eznvcc.vccs.edu:2443/login.aspx?direct=true&db=a9h&AN=9601151214&site=ehost-live
4. Genuis, S. J., & Kyrillos, E. (2017). The chemical disruption of human metabolism. Toxicology Mechanisms & Methods, 27(7), 477–500. https://doi-org.eznvcc.vccs.edu:2443/10.1080/15376516.2017.1323986
5. The Bottom Line on Boosting Metabolism: Exercise Works Best. (2004). Environmental Nutrition, 27(6), 7. Retrieved from https://search-ebscohost-com.eznvcc.vccs.edu:2443/login.aspx?direct=true&db=a9h&AN=13516317&site=ehost-live

Introduction

Yersinia pestis, the causative agent of plague, has been historically accountable for greater than 200 million deaths throughout three pandemics. Zoonotic maintenance of plague occurs through the ability of it propagation and circulation amongst rodent reservoir hosts and flea vectors. Upon consumption of an infected mammalian blood meal by a naïve flea, Y. pestis proliferates in the flea midgut. Y. pestis forms a biofilm in the flea proventriculus which prevents the passage of blood during subsequent feeding attempts. Moreover, the biofilm enhances the regurgitation of bacteria into the dermis of the mammalian host, thereby promoting the natural transmission of plague.

Y. pestis strains can be assigned to one of four biovars: Antiqua, mediaevalis, Orientalis, and Microtus. With biovar, Orientalis being the most recent evolutionary divergent variant believed to be the cause of the 3rd plague pandemic. It is the only variant known to have lost its capacity to ferment glycerol.

Fig1: Metabolisms in Different biovars

Prior transcriptomic analyses indicate that the components of the aerobic glycerol metabolic pathways are induced during multiple aspects of the Y. pestis infectious cycle. Aerobic glycerol metabolism is simulated during temperature shifts representing the transition from the flea vector (26°C) to the human host (37°C) and amid survival in the macrophage intraphagosomal environment.

Cell Structure

Yersinia pestis is a rod-shaped gram-negative bacterium that can also have a spherical shape. It falls under the Coccobacillus category of bacteria, with no spores. It is also covered by a slime envelope that is heat labile. When the bacteria are present in the host, they are nonmotile (incapable of self-propelled movement), but when isolated they are motile. It is a Facultative Anaerobic Organism and was first discovered by Alexander Yersin, a Swiss/French physician and bacteriologist from the Pasteur Institute. Similar to other Yersinia species, it tests negative for urease, lactose fermentation, and indole. The closest relative is the gastrointestinal pathogen Yersinia pseudotuberculosis, and more distantly Yersinia enterocolitica.

Pathology

Yersinia pestis interacts mainly with rodents such as rats and fleas. Through these carriers, Yersinia pestis is able to invade human cells and create diseases. Yersinia pestis are not rich in nutrients and can grow at temperatures ranging from about 26 Celsius to 37 Celsius.

Y. pestis causes diseases through the bite of an infected rat or flea, but can also be transmitted by air. Fleas can become infected by taking the blood of other infected animals. Y. pestis grows in the midgut and eventually blocks the proventriculus, starving the flea for blood. The insects attempt to feed more often but end up giving back infected blood into the wound of the bite.

The major defense against Y pestis infection is the development of specific anti-envelope (F1) antibodies, which serve as opsonins for the virulent organisms, allowing their rapid phagocytosis and destruction while still within the initial infectious locus. The immune mechanism against this disease is extremely complex and involves a combination of humoral and cellular factors. The host is immune to secondary virulent attack, the inoculum being eliminated as though the organisms were completely avirulent.

Metabolisms

(*Note: Yersinia pestis is a facultative Anaerobic organism which means that it gets ATP via Aerobic respiration if oxygen is present and if oxygen is absent it can switch to fermentation for its ATP requirements. *)

1. Glycolysis

Early studies of metabolism in YP focused on pathways of carbohydrate consumption. It was indicated that resting cells of YP utilize glucose primarily via the Embden-Meyerhof-Parnus pathway and that alternate pathways such as pentose phosphate pathway (PPP), do not contribute to this process. YP was observed to have the enzymatic capacity to catalyze all the constituent reactions of the glycolytic pathway.

In YP the traditionally recognized terminal step of this pathway, as catalyzed by the enzyme pyruvate kinase, might not be as extensively used for conversion of phosphoenolpyruvate (PEP) into intermediary metabolites of the citric acid cycle. Instead, YP tends to use the enzyme phosphoenolpyruvate carboxylase (Ppc) to carboxylate PEP into oxaloacetate. It was indicated that balance of oxaloacetate in YP 24 Metabolism of Yersinia pestis is a critical factor in cellular growth. Any metabolic perturbation that results in accumulation of oxaloacetate tends to encourage cellular growth while depletion of oxaloacetate tends to have the opposite effect.

This deduction is strongly supported by the observation that presence of CO2 or bicarbonate, stimulates cellular growth. In YP the reliance on Ppc could also alleviate some of the harmful consequences of aspartase deficiency. This is because absence of ASPA means that any process that would convert oxaloacetate into aspartate would be diverting metabolic carbons into the production of a dead-end product.

2. Pentose phosphate pathway

Initially, it was reported that all the constituent enzymes of PPP are present and active in YP and that during the growth phase this pathway is used to provide the pentose phosphates that are necessary for production of biomass. These conclusions were based on experiments where using 1- 14C-glucose with an avirulent strain of bacteria, it was discovered that the amount of 14C labeled CO2 released by growing YP was nearly 4 times greater than that liberated by resting cells. The presence of all enzymes of PPP was surmised since conversion of carbon 1 of glucose to CO2 results from oxidative decarboxylation by the pentose phosphate enzyme, phosphogluconate dehydrogenase.

However, later studies with the virulent Alexander stain showed that although cell-free extracts of YP include a number of different enzymes of the pentose phosphate pathway, the activity of glucose-6-phosphate dehydrogenase could not be detected. This observation has been confirmed in over 50 different YP strains spanning diverse geographic locations and all virulent biovars Contemporary sequence analyses of the YP genome have found a mutation in the gene encoding this enzyme (a proline substitution in amino acid 161), which supports the latter observation.

3. Anaerobic Metabolism

Under ordinary usual circumstances, YP grows in an oxygen-rich environment. These bacteria are facultative anaerobes and can also grow via fermentation. At 26°C, expressions of a number of genes associated with anaerobic energy production (such as fumarate and nitrate reductases) are upregulated. Although this could indicate that in the flea gut environment, oxygen is sparse and that YP’s metabolism shifts to anaerobic respiration upon transmission into this medium, absence of concomitant increases in expression of regulatory proteins response to anaerobic conditions have led to postulation that the increase in expression of above mentioned metabolic enzymes is primarily due increased cellular growth at 26°C (in comparison to LCR conditions).

Oxidative metabolism of glucose has been shown to produce very small quantities of organic acids, anaerobic carbon metabolism in contrast is highly inefficient. In the absence of oxygen, the metabolism of glucose will result in production of a number of organic acids, such as acetate, lactate, and formate. Overall, while oxidative metabolism of glucose results in nearly 60 percent assimilation of carbons into the cellular biomass, only 40 percent of the carbons are assimilated via anaerobic metabolism. As can be expected, resting cells in anaerobic environments cease to maintain a viable store of enzymes associated with TCA cycle and associated processes for oxidative mode of energy production.

4. Citric Acid Cycle & Oxidative metabolism

YP has a functioning TCA cycle. Observations indicate that given YP’s nutrient-rich environment, it frequently utilizes oxidative metabolism for its energy needs, for example, in vitro aeration of YP’s medium increases its growth rate. Growing YP rapidly oxidizes glucose and pyruvate while oxidative metabolism of acetate, succinate, fumarate, and malate proceeds at a lower rate. Finally, microarray gene expression data have shown that induction of cellular growth following the transition of cells from LCR to calcium-rich and 26°C conditions are accompanied with increases in expression of genes associated with oxidative modes of energy metabolism.

Even resting cells of YP, if grown aerobically, have a high rate of endogenous respiration (15-30% of respiration in presence of nutrients). This process proceeds independent of exogenous metabolism and thus the rate of O2 uptake and CO2 release is not a direct measure of the metabolism of nutrients from the media.

5. Glyoxylate Shunt

Although no enzymatic deficiencies have been reported, it was experimentally indicated that the YP citric acid metabolism does not proceed via the traditional reactions associated with the TCA cycle. Instead, the bacteria utilize the glyoxylate shunt as an alternate means. The glyoxylate shunt of TCA cycle is often used as an anabolic pathway for conversion of two-carbon compounds (such as acetate) into glucose via the metabolism of acetyl-CoA. Results support the notion that YP normally uses this pathway for its metabolic needs. First, it has been observed that YP can fully oxidize acetate with negligible production of α-ketoglutarate, and secondly, YP extracts have a limited capacity to convert α-ketoglutarate into succinate. Computational simulations of cellular metabolism also indicate that in rich media, there are a number of viable alternate pathways for the metabolism of oxaloacetate.

Enzymes essential for the glyoxylate bypass pathway are isocitrate lyase and malate synthase. Unlike E. coli and other Yersiniae, YP maintains significant levels of both of these enzymes during growth on hexose and pentose molecules. In YP, two forms of isocitrate lyase have been detected. One form is active during growth on acetate and absents when alternate carbon sources are utilized. The other form of the enzyme is not constitutive but can be detected while growing on a variety of different carbon sources. Therefore, it has been postulated that this form might have a significant role that is not associated with the enzyme’s traditional anaplerotic function

Finally, microarray analyses of gene expression associated with the glyoxylate shunt show that three of these genes (aceK, icl, and mas) are upregulated upon in 37°C LCR conditions. *(This could indicate that metabolism of two-carbon metabolites is more pronounced in the mammalian host; however, this hypothesis has not been verified) *. Thus, it can be argued that, although YP possesses the enzymatic means to proceed via traditional TCA cycle processes, it normally uses the glyoxylate shunt and bypasses some of the former’s reactions. The reason for deviation is not known. However, it has been hypothesized that given the glyoxylate shunt’s role as a means to convert two-carbon organic compounds into TCA cycle intermediates, the metabolic change could serve as a mechanism to replenish oxaloacetate that is withdrawn from cellular metabolism via its conversion into ASP. This further supports the assertion that absence of ASPA (which would have recycled ASP back into a TCA cycle intermediate) is a central factor in how the overall metabolism of the bacterium operates.

6. Amino Acid

i. Missing amino acid biosynthesis pathways

The principal pathway for incorporation of NH4 + into cellular metabolome and biomass occurs through the action of the enzyme glutamate dehydrogenase.

Following this initial step, the resultant glutamate (GLU) can be converted into other amino acids and intermediates of the TCA cycle through a number of different transamination reactions. Wild types ceased to grow in media which have low levels of ammonium salts as the sole source of nitrogen. It has been proposed that this mesotrophic deficit can be attributed to mutationally induced inactivation of glutamine synthase.

The loss of this metabolic capability is yet another indication that YP’s metabolism has begun to adapt to nutrient-rich environments. Furthermore, it indicates that the bacterium prefers to import a large portion of its amino acid nutritional needs from the surrounding medium. In line with this metabolic program, YP has lost the capacity to produce a number of amino acids and under normal conditions requires their import for cellular growth. YPS does not have an obligatory requirement for import of these amino acids and thus it can be deduced that YP’s transition to living in the nutritionally rich fluids has resulted in loss of capabilities which are essential for survival of its free-living progenitor.

ii. Use of amino acids as sources of carbon and nitrogen

Although only the import of some of the important amino acids is obligatory for cellular growth *(glycine (GLY) or threonine (THR), methionine (Met), phenylalanine (PHE), cysteine (CYS), isoleucine (ILE) and valine (Val)) *, a number of other amino acids can be metabolized by YP as carbon and nitrogen sources. For example, YP can rapidly catabolize SER via production of pyruvate and acetate intermediaries. Some studies have identified arginine (ARG) as one of the amino acids that cannot be catabolized by both YP and YPS. However, this metabolism is critical for YP’s transitions between flea gut and host environments. Microarray gene expression studies show that at 37°C, some of the genes involved in ARG biosynthesis (argABC) and its interconversion to GLU (astCADBE) are upregulated. The latter process releases CO2 and ammonia as by-products which can be interpreted as an added cellular need for ammonia as it transitions from flea gut to mammalian temperature. The need for ammonia might indicate increased amino acid interconversion. However, the consequences of raised intracellular ammonia concentrations are unknown.

iii. Dicarboxylic amino acids

Dicarboxylic amino acids serve a number of important roles in bacterial physiology. Aside from their role as building blocks for proteins, these molecules also act as amine donors and acceptors, as well as intracellular signaling metabolites. Furthermore, due to their facile conversion into intermediates of the TCA cycle, GLU and ASP can serve as important supplementary nutrients that provide a cell with both the carbon and nitrogen that it needs for proper growth. It has been proposed that a lesion in the metabolism of dicarboxylic amino acids might account for YP’s sluggish growth. The gene aspA which encodes for the enzyme aspartase plays a prominent role in catabolism of ASP. It catalyzes the deamination of ASP into fumarate, an intermediate of the TCA cycle. Absence of this enzyme coupled with low turnover rate for some of the other enzymes involved in ASP and GLU metabolism severely limits the capacity of YP to convert these amino acids into bio-energetically useful metabolites.

Under some conditions in YP, ASP tends to be a dead-end metabolite. For example, the LCR of YP results in excretion of ASP as a by-product of catabolism of exogenous glutamate. This metabolic feature results in a loss of 4 carbon nutrients which could have entered the cellular carbon metabolism via production of fumarate and oxaloacetate. However, compensation for this nutrient loss explains the stimulatory effect of CO2 on the growth of YP. CO2 and bicarbonate can be converted into oxaloacetate through carboxylation of phosphoenolpyruvate by the enzymes phosphoenolpyruvate carboxykinase and phosphoenolpyruvate carboxylase.

Accordingly, the absence of ASPA in YP means that the primary pathway for conversion of dicarboxylic amino acids to TCA intermediates is the NADP + dependent deamination of GLU to -ketoglutarate by glutamate dehydrogenase. Therefore, although the specific activity of glutamate dehydrogenase in YP is comparable to that of YPS, the excessive metabolic burden can overwhelm the capacity of this enzyme to metabolize dicarboxylic amino acids. Additionally, use of NADP+ by glutamate dehydrogenase complicates the situation and further strains YP’s metabolic mechanisms. Due to YP’s deficiencies in the aerobic portion pentose phosphate pathway, the cell is forced to rely heavily on the activity of transhydrogenase enzyme to oxidize the resulting NADPH before it can be used for oxidative phosphorylation.

*Some Other Metabolisms include Nucleotide metabolism, Fatty acid metabolism, Iron Transport metabolism, and Transmission Factor metabolism. These metabolisms show no notable effects on the growth of the bacteria but have different functions and is currently being studied.

References

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Discussion

In the present study, we investigated the effects of lifelong, moderate-intensity exercise on blood metabolites through an NMR-based metabolomics approach. By comparing a lifelong exercise group, two long-term exercise groups, and a group that did not exercise, we found that moderate-intensity exercise has a strong effect on the blood metabolome up until midlife. From midlife to elderhood, the effect of aging becomes stronger than that of exercise.

This unexpected finding comes in agreement with a study conducted by Falegan et al. (2016) who found that aerobic capacity could mitigate some but not all age-related changes in the metabolic profile of rats. In a very recent study Deda et al. (2018) detected changes after short-term and lifelong exercise in blood metabolites of female rats using LC-MS analysis, however, a limitation of this study is that no pre-exercise comparison of the exercise and non-exercise groups is shown. Most exercise metabolomic reports show the detected changes in human blood metabolome due to either short- or long-term exercise of young (Pechlivanis et al. 2013), aged (Mukherjee et al. 2014), or all ages individuals (Lewis et al. 2010). A few studies have shown the lifelong effect of exercise on cognitive processes (Pietrelli et al. 2018), cardiac function (Gama et al. 2010, Rockstein et al. 1981), and the antioxidant defense in many tissues (Cui et al. 2009, Gündüz et al. 2004), however, these studies did not involve any metabolomic analyses.

Thus, the uniqueness of our study is that the effect of lifelong exercise on the entire blood metabolome was analyzed on all groups pre and post-exercise by 1H NMR metabolomics analysis. NMR is a powerful metabolomics tool, as it can detect analytes which are difficult to be found with other technologies (Pechlivanis et al., 2010). Hence, the investigation of the effects of lifelong exercise and aging on blood metabolites through an NMR-based metabolomics approach may provide an insight in understanding better some aspects of exercise biochemistry. The relevance of the study lies in the fact that lifelong exercise has not been fully examined in the entire blood metabolome, possibly due to methodological difficulties.

Exercise and aging result in changes in numerous metabolites involved in different metabolic pathways. The results of our study are summarised in Figure …. The changes in the metabolites will be discussed in the alphabetical order of the metabolic pathway that they are involved for convenience.

Amino acid metabolism

The literature states that both exercise and aging result in fluctuations of amino acids, however, exercise tends to increase the total content of amino acids (Takeshita et al., 2011). This statement is somehow supported by our findings on the total content of amino acids, in which only group C, ie. the group that did not exercise at all, showed a significant decrease in the total content of amino acids from both 3 to 12 and 3 to 21 months.

Correlations of metabolites involved in amino acid metabolism were found at 12 months both because of exercise and aging. Correlations were also found at 21 months in groups A, B, and C. Aging resulted in a decrease in five (asparagine, aspartate, glutamate, glycine, and serine) out of the seven glucogenic amino acids that we identified. On the other hand, alanine and histidine, which are the remaining two glucogenic amino acids that we identified, increased. Group C, the group that did not exercise at all, was the only group that showed a decrease in the total content of glucogenic amino acids. These results could imply an aging-induced decrease in the dependence on glucogenic amino acids. In normal aging cell metabolism is reduced. However, no studies were found to support this finding, on the contrary, studies have shown that intense exercise results in a decrease in glucogenic amino acids, which may correspond to enhanced gluconeogenesis (Takeshita et al., 2011). At this point, we could hypothesize, that aging had a similar effect to that of intense exercise on glucogenic amino acids. Interestingly though, the levels of aspartate were higher at 21 months in the groups that exercised at the second half and the levels of glutamate were higher at the same age in the groups that exercised at the first half. This could imply an effect of lifelong and long-term exercise on aspartate and a prolonged effect of long-term exercise on glutamate.

Furthermore, group B, the lifelong exercising group, showed a significant increase in the total content of ketogenic amino acids on the second half of its life. It is of interest though, that the lifelong exercise group was the only group that had significantly higher values of lysine at 21 months. Group C, however, showed a significant decrease in the same group of amino acids on the first half of its life. This finding could imply that aging decreased the content of ketogenic amino acids. This last observation is supported by Houtkooper et al. (2011) and Okuda et al. (1987) who concluded that there is an aging-related diminished ketogenic capacity. Oddly enough though, the two exclusively ketogenic amino acids, leucine, and lysine were found to increase due to aging at 21 months. However, Hourkooper et al. (2011) also noticed aging-induced increases in lysine.

Another perspective concerning the amino acid metabolism is that two branched-chain amino acids (BCAA; isoleucine, leucine) and an aromatic amino acid (tyrosine) had higher values at 21 months. Elevated levels of these amino acids in the circulation are known to be significantly associated with age-related disorders, such as insulin resistance, which could lead to type 2 diabetes, and cardiovascular dysfunction (Falegan et al. 2016). Contrary to our findings are the results of Chaleckis et al. (2016) article, which identifies age-related differences in human blood metabolites, and it states that leucine and isoleucine were less abundant in elderly individuals. This difference could have either resulted due to differences in human and rat blood metabolome, due to a limitation of the study that it was not longitudinal, so different subjects were used to compare young and aged individuals, or according to Falegan et al. (2016) it could show that our rats were suffering from age-related disorders. Glycine, whose levels also decreased due to aging, is also found to be reduced years before the expression of prediabetes or type 2 diabetes (Klein et al. 2016).

Ammonia recycling

Exercise and aging resulted in correlations of many metabolites involved in ammonia recycling at 12 months. Three of them showed an aging-related significant decrease (asparagine, glutamate, serine). Decreases in asparagine, glutamate, and serine were also found by Houtkooper et al. (2011), who published changes in biomarkers of aging. Correlations in the same metabolic pathway were also found at 21 months in groups A, B, and C.

Betaine metabolism

A moderate correlation between two metabolites (dimethylglycine and betaine) involved in betaine metabolism was found in the lifelong exercise group at 21 months. Betaine is a methyl derivative of glycine and is metabolized to dimethylglycine and sarcosine (Cholewa et al., 2014). It is examined mainly as a dietary supplement, as improvements in lactate metabolism and hydration have been reported. However, little can be discussed about this pathway in our study.

Bile acid metabolism

A moderate correlation between two metabolites (glycine and taurine) involved in bile acid metabolism was found in the exercising groups at 12 months. At 21 months only group B showed a strong correlation between two metabolites involved in this specific pathway. Bile acid metabolism, which is the main way of eliminating excessive cholesterol in liver, can be activated by exercise training through the excretion of fecal bile acids (Farahnak et al., 2017).

Carbohydrate and lipid metabolism

Age resulted in correlations of metabolites involved in carbohydrate metabolism at 12 months. Of those metabolites, glucose showed a significant increase due to age. At 21 months correlations were found in groups A, B, and C. The increased levels of mannose, glucose, and glycerol at 12 months of age could possibly suggest enhanced carbohydrate and lipid metabolism up until midlife. Mannose, however, significantly decreased from 12 to 21 months and the exercising groups had higher values at 12 months. Pyruvate was also found increased at 21 months, suggesting enhanced glucose metabolism. Our results, in conjunction with another research, imply that glucose may be preferred over fatty acids as a fuel in older individuals, and is presumably the result of age-related changes in skeletal muscle’s respiratory capacity (Mittendorfer & Klein, 2001). It is of interest though, why these energy sources were not affected by exercise.

Gluconeogenesis is known to be activated in conditions of low glucose concentrations in plasma and intense exercise. However, many are the studies that claim that gluconeogenesis and blood glucose produced through it increases with age (Feng et al., 2016, Hachinohe et al., 2013, Lin et al., 2001). Specifically, a shift of energy metabolism away from glycolysis and towards gluconeogenesis is noticed (Lin et al., 2001). Feng et al. (2016) explain that gluconeogenesis might be elevated due to an increase in alanine (in our study, alanine indeed increased due to aging) and glutamine caused by sarcopenia, a disease by which muscle is lost in aging humans and animals. It is of interest though why the organism acts as if it is glucose-deprived when glucose uptake from brain and muscles in aged organisms is decreased. According to Feng et al. (2016), the increased demand and supply of glucose, combined with a reduction in usable glucose could lead to its disrupted homeostasis in aged organisms.

Citric acid cycle

Correlations between metabolites involved in the citric acid cycle (CAC) were seen at 12 months due to aging. Succinate, which is a TCA cycle intermediate, was affected by both aging, which decreased its levels, and exercise, which increased its levels. Huffman et al. (2014) support these findings, as they state that exercise training increases succinate dose-dependently. The CAC is an essential metabolic network in all oxidative organisms that provides anabolic processes in order to generate energy. It is also a functional target in the aging process in mammals (Yarian et al., 2006). Studies have identified an intricate link between CAC and reactive oxygen species (ROS) homeostasis, as the inefficient transfer of electrons results in generation of toxic ROS, which may help explain various metabolic diseases and aging (Mailloux et al., 2007, Yarian et al., 2006). Even subtle changes in just one metabolite could affect CAC intermediates and consequently affect signal transduction mechanisms (Yarian et al., 2006).

Ketone body metabolism

The evidence of moderately correlated metabolites involved in ketone body metabolism, in the exercising groups, as well as the increase of isobutyrate, a derivative of 3-hydroxybutyrate, which circulates sources of energy, in the same groups at 12 months, could possibly suggest an exercise-related activation of the specific pathway through periods of critically reduced CHO availability. However, at 21 months correlations of metabolites involved in ketone body metabolism were only found in group C, the non-exercising group. Ketone bodies are free fatty acid derivatives, which are converted to acetyl-CoA, via mitochondrial b-oxidation, and are used as a glucose-sparing energy source (Newman & Verdin, 2014). The literature states that ketogenesis is a critically important adaptive response, which during an energy crisis provides a substrate for brain (Evans et al., 2017).

Glucose – Alanine cycle

The exercise-related correlations of metabolites involved in the glucose-alanine cycle show its contribution to the energy demands of the exercising groups at 12 months. The exercise seemed to play a role as well at the correlations found at 21 months in groups B and D at the same pathway. In this pathway, lactate is formed from glucose and alanine through their conversion into pyruvate which is further reduced to lactate (Adeva-Andany et al., 2014). However, since it is a time-consuming process, the specific cycle is of limited importance to any type of exercise effort.

Phosphocreatine (CP)

In our study, we found low levels of CP at 21 months which suggests decreased CP re-synthesis when aging. In the review of Dalbo et al. (2009), it is stated that due to sarcopenia, the intramuscular CP levels are 5% lower in older compared to younger individuals. Although we did not find any significant changes due to exercise, it is important to note that from 12 to 21 months the lifelong exercise group had the least reduction in CP values (1%), group A, the group that exercised at the first half had a 7% reduction, group D, the group that exercised at the second half had a 16% reduction and the group that did not exercise at all, had the most reduction (18%).

Pyruvate metabolism and acetate

Acetate and lactate were found to be moderately correlated at 12 months in the exercising groups. Both metabolites take part in reactions involved in pyruvate metabolism. For example, in order to permit pyruvate, formed by glycolysis, to be fully oxidized by the TCA cycle, a molecular switch that interconverts acetyl-CoA and acetate needs to occur (Wolfe, 2005). This switch supplies the cell with opportunities to recover NAD+ and generate ATP.

Acetate, which is an important source of acetyl-CoA, increased up until midlife, and then it started decreasing until it reached significantly lower volumes at 21 months than at any other age point. Exercise, at the first half, helped at maintaining higher volumes at 12 months. This finding is supported by the fact that acetate levels also rise when fatty-acid oxidation rises (Shimazu et al. 2010). Formate had a similar trend to acetate, as it decreased due to aging and it increased due to exercise. The two metabolites had also a significant positive correlation. However, no studies were found to support these results. Significant negative correlations were also found between acetate and pyruvate, and formate and pyruvate. This could imply an important contribution of these metabolites in central metabolic pathways. Shimazu et al. (2010) speculate an important and underappreciated role of acetate metabolism in aging, due to its metabolism regulation by sirtuins, whose role are also important in the regulation of aging and longevity. Thus, further research between the relationship of acetate, formate, pyruvate, and aging is suggested.

Redox metabolism

A decrease in NAD implies a declined redox metabolism in the elderly, this result is supported by Gomes et al. (2013), who also mentions that the impairment of oxidative phosphorylation function during aging may have as a result depletion of the nuclear NAD pool. It is important to study redox metabolism as reduction and oxidation reactions are involved in our everyday life and are principal sources of energy. Although no oxidative stress biomarkers were identified, an interesting finding was that total glutathione of the lifelong exercise group and the group that exercised at the first half had lower values at both 12 and 21 months. Unfortunately, this result cannot lead us to a safe conclusion as we do not have values for GSH and GSSG separately.

Transcriptional and or translational pathways

Correlations of metabolites involved in transcription and translation pathways were also noticed due to exercise and aging at 12 months, as well as all four groups at 21 months. Specifically, threonine and asparagine, which are involved in transcriptional and translational pathways were found deceased due to aging, and cytidine was found increased. Group B and D showed a significant increase in tyrosine and only group B showed a significant decrease in threonine. Merry & Ristow (2016) mention changes in transcriptional responses due to the exercise-induced mitochondrial stress. Also, an increase in the translation rate of proteins is also noticed by exercise. Robinson et al. (2017) examined the effect of three different exercise modalities (HIIT, resistance training, and combined training) on the translation of mitochondrial proteins and two of them (HIIT and combined training) improved aerobic capacity, associated with their enhanced translation. As far as aging is concerned, it interferes with the transcriptional machinery in multiple ways, increasing diversity and heterogeneities (Alfego et al., 2018). Moreover, age is associated with changes in transcription regulatory networks, which may affect genes related to immune and defense responses as well as synaptic and neural activities (Ianov et al., 2016) and impact the function of cells or tissues and give rise to aging phenotypes and diseases (Buth & Brunet, 2017). Although aged organisms are more sensitive to errors in protein translation, studies have not detected a significant increase in mistranslated proteins during aging and cellular senescence (Ke et al., 2018). Nevertheless, protein synthesis decreases significantly (from 20 to 75%) with increasing age (Gonskikh & Polacek, 2017). This last statement is supported by Anisimova et al. (2018), who also mentions that aging affects the rate and type of damage accumulation in various organs and tissues having as a result altered translation efficiencies and changes in protein synthesis.

Nonetheless, exercise seemed to play an important role in maintaining lower body weight. This finding is supported by the fact that groups A and C, which did not exercise at the second half, weighed significantly more than the remaining two exercising groups, and the lifelong exercise group was the only group which did not show a significant increase in weight from midlife to elderhood. Specifically, at 21 months the lifelong exercising group weighed 10% less than the lifelong sedentary group and 6% less than the midlife to elderhood sedentary group. Garvey et al. (2015) also found that 8 weeks of activity significantly decreased body weight gain compared to rats without running wheel access. Furthermore, taking into account the previous results with the results of food intake which showed that group A had a significant increase in all periods except for the period that it did not train, which is from 12 to 21 months, in which it showed a significant decrease; as well as the results of the lifelong exercise group which showed a significant increase in all periods and group D which only showed an increase from 3 to 21 months and not between the first period of its life as it did not train at that time, we could hypothesize that the energy expenditure of the exercising rats was greater due to exercise.

Conclusion

Both exercise and aging had an impact on metabolites involved in different metabolic pathways. The results were mixed, some were expected, but others unexpected. The main outcomes of the study were that when aging the organism acts as if it is glucose-deprived and exercise does no longer affect the energy sources. However, exercise seemed to have a protective role over CP deprivation which is highly correlated with sarcopenia. Moreover, due to the greater energy expenditure of the exercising rats, their body weight was maintained lower until the end of their life. On no account do we diminish the importance of exercise at points that it might seem to have unexpected or no effects at all, on the contrary, we encourage people to become or remain active at all ages. The intensity and type of exercise play a big role in the outcome and effects of it and this could be a question open to future research. Furthermore, a similar experiment with caloric restriction and sampling of acute exercise at more age points could present notable results. Other recommendations for future research may be the exploration of the connection and pathways of acetate, formate, and pyruvate when exercising and aging, whose results were rather interesting.