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The Aging Process - The Biology of Aging
Since the beginning of mankind humans have strived to live eternally, an attribute only possessed by the Gods. People's health deteriorates as they get older, starting already in their 30s'. Understanding the processes of aging can enable informed lifestyle changes to greatly extend life- and health-span.
Aging is a biological process involving structural and functional changes in all cells and organs. Historically, our lives used to be far shorter than they are today. Even in the 1800s the average life expectancy was less than 40 years, but medical breakthroughs and improved quality of life greatly raised this during the next 150 years. The worldwide life expectancy in 2020 was 72.6 years, which is greater than any country's life expectancy in 1950.
When it comes to your age, there are two figures to consider: your biological age and your chronological age. Your chronological age is calculated based on how many birthdays you've had, or how many years you have lived. Your biological age is determined by the way your body functions and the amount of wear and tear your cells have encountered. You can't modify your chronological age (the number of years you have lived), but you can dramatically slow down your biological aging, and even reverse it to some extent.
Are you curious about your biological age? You can do this through DNA methylation with a kit developed by epiAge. This low cost test is easy to perform and accurate, and is integrated with an App that will provide recommended lifestyle behaviors by major US national medical associations. These recommendations are based on what “science” knows today, and are updated as science is advancing.
The wear and tear of your cells, tissues and organs define your biological age. Researchers have developed multiple techniques to assess biological age. They've also established that biological age is a greater predictor of lifespan than chronological age. So, if you take good care of yourself, you may be 50 years old chronologically while being 30 years old biologically. Conversely, if you have an unhealthy lifestyle, you may end up being 50 years old biologically by the time you have lived 30 years.
At a microscopic level, each cell in the human body performs its normal metabolic activities. The by-products of these activities accumulate over time and become toxic to the organism, resulting in gradual degeneration, greater frailty, and eventually death. Our aging timetable is also influenced by interactions between our genes and the environment. But our genes may only account for up to a quarter of our natural longevity predisposition due to the mechanism of epigenetics: the environment can influence the activity of our genes. Therefore, whether we are going to live a long and healthy life is not pre-determined, but mostly up to us and not our genes.
The aging body
Aging is a multifaceted and complex process that leads to a progressive loss of biological functions in an organism. It generally first appears after adolescence and can eventually results in disability and death. Traditionally, researchers have concentrated their efforts on studying how physiological capabilities degrade with age, with little attention paid to the reasons, or biological processes, of the actual aging. It has been estimated that the average lifespan of humans would increase by 12 years if scientists discovered medicines that could cure all major chronic degenerative illnesses. However, people would still die as a result of aging-related deteriorations. Defects created in the human body as a result of the aging process appear early in life. Both the number of afflicted cells and the extent of damage are minimal in the early years, but after reaching adulthood, when one's health, strength, and appearance are at their peak, the indications of aging begin to appear. All physiological processes begin to deteriorate after puberty (e.g. the maximum lung, heart and kidney capacities are decreased, the secretion of sexual hormones is lowered, skin wrinkling, etc). The biological and cellular mechanisms that cause aging are likely to involve a combination of complex and interrelated factors, including: oxidative stress–induced protein and DNA damage in conjunction with insufficient DNA repair resulting in genome instability; changes in fatty acid metabolism such as excessive free fatty acid release into plasma resulting in insulin resistance; buildup of by-products from metabolism including glycation end-products, amyloid, as well as proteins interfering with normal functions of cells; noninfectious chronic inflammation; changes in hormonal systems; and cell death leading to a decrease in muscle mass, neurons and a general deterioration of tissue and organ functions.
Aging happens at multiple levels, from cells to organs and entire physiological systems. Different organs and physiological systems do not necessarily age at the same rate. For example, the respiratory system of smokers and skin of people getting too much exposure to the sun may age faster than other organs. When it comes to anti-aging and maintaining youthfulness, many people pay an excessive attention and importance to appearances, basically our looks. We want to look and appear as youthful, rather than also feel agile and youthful. Therefore, much emphasis has been given to various anti-aging skin and hair products and procedures since they would maintain a young appearance, even if the rest of the body is ageing at an alarmingly fast rate because of an unhealthy lifestyle. Adopting a more holistic approach to anti-aging where lifestyle changes and technologies are used to halt aging in the entire organism, from the inside out and from the outside in, is preferred, and it will also ensure a youthful and healthy appearance. Many anti-aging approached also work synergistically, so the overall benefit of applying multiple interventions is greater than applying them individually.
The aging cells
Cells can be considered the smallest units of life because they are the basic biological, structural, and functional units, or building blocks, of organisms. The nucleus of our cells contains our DNA, or genetic material, which encodes and directs biological processes. The cytoplasm surrounds the nucleus, which is contained by the cell membrane. The cytoplasm includes biomolecules like proteins and organelles that perform activities including energy generation, detoxification, and immunity to pathogens. However, cells eventually lose their capacity to operate as they age. As a natural part of the body's operation, old cells must eventually die, many times because our DNA instructs them to do so. Basically, the cells' genes program a mechanism that, that when activated, causes the cell to die. Apoptosis, or programmed death, can be considered a form of cell suicide. One of the triggers of apoptosis is a cell's ageing; to make way for new cells, old cells must die. An excessive number of cells, as well as possible cell damage, are other causes for cells to die. As cells get older they also die because they can only divide so many times. Genes are in charge of setting this limit. A structure in our DNA called a telomere is involved in the process that restricts this cell division. Telomeres, which hare the ends of our chromosomes, are responsible for moving the genetic material of the cell in preparation for cell division. Telomeres shorten a little each time a cell divide. The telomeres eventually shorten to the point that the cell can no longer differentiate. Senescence then occurs when a cell begins dividing. Harmful substances such as radiation, sunlight and chemotherapy drugs can be toxic and harm cells. Certain by-products of a cell's own normal activities may also damage it. When cells generate energy, they produce by-products known as free radicals which are toxic.
The aging organs
The health of organs is determined by the health of the cells inside them. As cells get older they have a lower ability to perform essential functions and survive. Furthermore, cells die and are not replaced in certain tissues, resulting in a reduction in the overall number of cells. As the body ages, the number of cells in the testes, ovaries, liver, and kidneys declines dramatically. An organ cannot perform normal functions when the number of cells becomes too low. As a result, most organs become less effective as people age. Not all organs, however, lose a significant number of cells. One example is the brain. Healthy people do not lose many brain cells as they age. People who have had a stroke or who have a condition that causes the gradual loss of nerve cells (neurodegenerative disorders), such as Alzheimer's disease or Parkinson's disease, experience significant brain cell losses. A deterioration in the function of one organ, whether due to a disease or simply aging, may have an effect on the function of another organ. If atherosclerosis narrows blood vessels to the kidneys, for example, the kidneys will perform less well because blood flow will be reduced.
The musculoskeletal system is often showing the first symptoms of aging. Early in life, the eyes, followed by the ears, begin to shift. Most internal functions deteriorate as people age. Most bodily functions reach a plateau at about the age of 30 and then begin a slow but steady decline. Despite this decline, however, most functions continue to be adequate because most organs begin with much more functional capacity than the body actually requires (this is referred to as functional reserve). If half of the liver is lost, for example, the remaining tissue is more than sufficient to preserve normal functions. As a result, much of the loss of function in old age is due to diseases rather than natural aging. However, despite the fact that most functions remain adequate to sustain life, the loss in function makes older people less able to cope with a variety of stresses, such as strenuous physical exercise, sudden temperature fluctuations, and infections and illnesses. Under conditions of stress, certain organs are more likely to fail than others. The heart and blood vessels, the urinary organs (such as the kidneys), and the brain are among these organs.
Hormonal and endocrine decline
The endocrine system is made up of glands and organs that produce and release hormones that regulate and control numerous bodily processes. Hormones are chemical compounds that influence the activity of other organs in the body; they are essentially messengers that govern and coordinate actions throughout the body. The blood concentration (level) of most hormones declines as people become older, but other hormones stay the same or even rise, compared to younger individuals. Endocrine function also often declines with age. Menopause is for example caused by a decrease in estrogen levels in women. Testosterone levels in men often decline over time. Human growth hormone (HGH) levels also decline with age and this can lead to a loss of muscular mass and strength, as well as a decline in other systems. Melatonin deficiency may have a role in the loss of regular sleep-wake cycles (circadian rhythms) as people age. As a result of these hormonal changes, elderly persons are more likely to experience sleep disturbances, have a lower metabolic rate, lose bone density, gain body fat, and have higher blood glucose levels.
Aging-causing processes
Inflammation
Inflammation (swelling), which is a natural element of the body's healing process, aids in the battle against injury and infection. Unfortunately, it does not only result from injury or infections. When the immune system is activated without an injury or infection to fight, an inflammatory response can ensue where immune system cells, that normally protect us, begin to kill arteries, organs, and joints because there is nothing to mend. An unhealthy diet, lack of exercise, and excessive stress can all result in an induction of inflammation. Inflammation is an essential process of our immune system that defends against a variety of infections, as well as cancer by identifying and eliminating cancer-causing cells. Inflammation is also part of tissue healing. So overall the advantages of inflammation outweigh the hazards is can cause. When inflammation is controlled, by being engaged transiently in response to an infection or injury, it has a beneficial effect on our health. However, it is important that the inflammatory response returns to a baseline “resting” condition once the infection has been eliminated. When inflammation becomes persistent (chronic inflammation) it will do harm to cells, organs and entire physiological systems, stressing them and speeding up the aging process. Chronic inflammation results in conditions such as sarcopenia (loss of muscle mass and strength), weight loss, loss of agility, atherosclerosis, cancer, cardiovascular disease, cognitive deterioration, depression and increased fatigue, all of which contribute to accelerated ageing and a general health impairment. Older people develop a pro-inflammatory (inflammation promoting) state marked by high amounts of pro-inflammatory molecules in cells and tissues This condition is also known as inflammaging.
Risk factors and causes of inflammaging
While the core causes of inflammation, as well as the processes that link inflammation to a variety of health effects, remain poorly understood, studies have linked it to the function of our immune system. As we age the regulation of our immune system become faulty (dysregulation) and this results in high blood levels of various pro-inflammatory immune system molecules, even in absence of an infection. At the same time, this immune dysregulation results in a diminished capacity to develop an efficient immune response (or inflammatory response) to infectious agents. So, despite the immune systems importance as a defense mechanism against viruses, bacteria and other infectious agents, when the immune response (or inflammatory response) lasts for a long time in absence of infection, it becomes harmful to one's health.
Obesity causes inflammation
Up to 50% of fatalities globally are caused by disorders connected to chronic inflammation, and clear relationships have been established between obesity, inflammation, and the metabolic syndrome. Insulin resistance, metabolic syndrome, and type 2 diabetes are all directly influenced by metaflammation, the metabolic inflammatory condition linked to obesity. A low-level chronic inflammation in metabolic tissues, such as the brain, liver, pancreas, and adipose tissue, are characteristic of this condition. People who have been told by a doctor to lose extra weight have been found to experience reduced inflammation and increased insulin sensitivity.
Microbiota and gut permeability can cause chronic inflammation
Our gut bacteria, or intestinal microbiome, play a very important role in maintaining good health. As we grow older, the composition of the intestinal bacteria changes, and unfortunately these changes frequently involve the loss of beneficial microbes that defend against harmful bacteria and maintain a healthy state, and acquisition of harmful bacteria that compromises the integrity of the gut barrier and therefore increases the permeability of the gut. This enables bacteria and their products to pass through into the circulatory system causing inflammation. Certain harmful bacteria, or pathobacteria, become pathogenic in a proinflammatory environment and can therefore further deteriorate the health of people suffering from chronic inflammation. Altogether, these processes contribute to a chronic pro-inflammatory condition. Unhealthy changes in the intestinal microbiota (or dysbiosis) seems to be more frequent in obese people and those suffering from type 2 diabetes. Such changes of the gut microbiota have also been linked to an impairment of the immune system and can significantly compromise healthy aging. The use of probiotics, prebiotics, or a combination of the two, can improve microbiota composition and thereby enhance gut barrier integrity and reduces inflammation. Some studies have suggested that this approach can lower systemic/overall inflammation and the advancement of visceral obesity.
Cellular senescence as a mechanism of inflammaging
Senescence of cells is a term that refers to the aging of cells that eventually leads to their death. Many factors can cause cell senescence, including telomere shortening, chronic DNA damage, oncogene activation or inactivation, epigenetic modifications, mitochondrial malfunction, and environmental exposure to toxins and irradiation. Cellular senescence is a cancer suppressor mechanism that is characterized by a loss of ability to divide and an enlargement of the cells. Importantly, the accumulation of senescent cells in many organs is a key promoter of inflammation. Cellular senescence appears to be linked to aging, inflammation, cardiovascular disease, and decreased physical function in older people, making cell senescence a viable contender as a mechanism for inflammaging. Senescent cells appear to secrete a wide spectrum of pro-inflammatory molecules that can promote the development of senescence in neighboring cells, and senescent cells therefore accumulate rapidly in numerous organs and tissues as people age.
Impaired recycling and removal of degradation products causes inflammation
Despite the human body's apparent stability, a huge turnover of molecules, microorganelles, cells, and other cellular components happens on a continuous basis throughout life. A sophisticated and tightly controlled molecular machinery regularly scans cellular components and deals with the repair or removal of biological trash, as well as damaged or misplaced molecules. A process called autophagy (self-eating from Greek) will recycle worn-out molecules and organelles of cells. This process is part of our immune system that recognizes “trash” molecules and degrades them. Stressed cells that undergo necrosis (death) release chemicals and molecules, such as free radicals for example, that need to be eliminated quickly since their build up can lead to inflammation. Inflammageing is thought to arise from an age-related imbalance between the production and disposal (autophagy) of cellular waste.
Chronic infections cause inflammation
Chronic infections such as mouth infections, silent chronic infections of the urinary system, and intestinal infections can cause a long-term inflammatory response because these infections continuously stimulate the immune system. Treatment for these infections can decrease inflammation and may have a number of long-term benefits in addition to the immediate relief of symptoms. There are numerous and quite diverse causes of inflammation and several processes are most likely additive and linked, working in various combinations towards creating an inflammatory state.
Unhealthy diet promotes inflammation
A major source of inflammation is from the foods we consume, and the most potent inflammation promoting foods are:
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Food rich in refined carbohydrates: i.e. pastries, pasta, white rice, crackers, flour tortillas, biscuits and white bread.
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Fried foods: i.e. French fries, donuts, fried chicken and mozzarella sticks.
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Sugar-sweetened beverages: i.e. sweet tea, energy and sports drinks and soda.
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Red meat such as steaks, chops, and burgers.
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Processed meat: i.e. sausages, hot dogs, bacon, beef jerky, canned meat, salami, and smoked meat.
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Junk food: i.e. fast food, convenience meals, potato chips, pretzels.
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Food rich in trans fats: i.e. shortening, partially hydrogenated vegetable oil, margarine and lard.
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Alcohol.
Oxidative stress
When oxygen is metabolized during regular metabolic activities, unstable molecules known as "free radicals," are produced by the cells. These free radicals steal electrons from other molecules, such as DNA and essential proteins. Antioxidants, on the other hand, are produced by cells and neutralize free radicals. The body is capable of maintaining a balance between antioxidants and free radicals. Some free radicals may also be tolerated by the body to function properly. However, an imbalance of free radicals and antioxidants will produce an excess of free radicals that cause chronic oxidative stress, which can lead to cell and tissue damage. Oxidative stress-related illnesses include cancer, diabetes, heart attacks, strokes, atherosclerosis, and ischemia/reperfusion injury, asthma, male infertility, chronic fatigue syndrome, chronic inflammation, rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, cataracts and neurological disorders. Several studies have highlighted the role of oxidative stress in the development of neurodegenerative diseases including Alzheimer's and Parkinson's. Because brain cells require a large amount of oxygen to function, free radicals are produced when brain cells engage in metabolic activity. Excess free radicals can damage structures inside brain cells and potentially induce cell death, raising the risk of Parkinson's disease. Oxidative stress may also alter amyloid-beta peptides in a way that aids in the formation of amyloid plaques in the brain which is an important indicator of Alzheimer's disease.
However, oxidative stress has a wide range of impacts that aren't necessarily damaging. Physical activity-induced oxidative stress, for example, can promote tissue development and drive antioxidant formation. Mild oxidative stress may also help to protect the body against infection and illness. Long-term oxidative stress, on the other hand, harms the body's cells, proteins, and DNA. This can speed up the aging process and have a role in the development of a variety of diseases. Oxidative stress can also provoke an inflammatory response which creates more free radicals, leading to further oxidative stress, thereby creating a vicious cycle. Chronic inflammation caused by oxidative stress can, in turn, lead to a variety of adverse conditions.
Oxidative stress may play a role in the development of a range of conditions, including:
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Cancer
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Alzheimer’s disease
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Parkinson’s disease
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Diabetes
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Cardiovascular conditions such as high blood pressure, atherosclerosis, and stroke
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Inflammatory disorders
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Chronic fatigue syndrome
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Asthma
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Male infertility
Factors that may increase a person’s risk of long-term oxidative stress include:
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Obesity
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Diets high in fat, sugar, and processed foods
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Exposure to radiation
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Smoking cigarettes or other tobacco products
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Alcohol consumption
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Certain medications
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Pollution
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Exposure to pesticides or industrial chemicals
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Smoking
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Strenuous exercise
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Psychological and emotional stress
DNA damage
DNA damage is caused by a variety of factors, including intracellular metabolism, replication, and toxic chemicals and radiation. If the damage is not corrected, it may cause alterations or mutations in the cells genetic material leading to a decline in viability or uncontrolled proliferation. Therefore, DNA damage appears to impact the majority, if not all, elements of the ageing process, making it a potentially unifying cause of aging. The DNA damage theory of aging suggests that aging is caused by the buildup of naturally occurring DNA damage that is not repaired. DNA damage can cause aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction). Several studies have shown that poor DNA repair causes premature aging by allowing more DNA damage to accumulate, and that better DNA repair promotes longer life.
Telomere shortening
A telomere is located at a chromosome's end and preserves the chromosome from damage. Telomeres get shorter every time a cell divide, and will eventually shorten to the point that the cell can no longer divide. Hence, successive telomere shortening will eventually lead to senescence, thereby compromising an individual's health and longevity. Shorter telomeres have been linked to an increased risk of illness and a decreased probability of survival, and the telomere length determines the lifespan. Cellular senescence and apoptosis are caused by the continuous shortening of telomeres.
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