Recently I have seen an old lady teasing an young girl who became breathless after climbing up a few steps.  "Look I am 78. But still I can climb steps with ease. I can go anywhere I want without any difficulty. I don't have joint pains like you people have. What are you eating? Rubbish! Ha, ha,ha".

To tell you the truth I really got irritated with this ridicule. Because  not everybody will be alike and different people will age differently 'biologically'. Yes, what you eat has some effect on your health but that is not the only reason why you 'age sooner than you should be aging actually'.

People age in different ways. Biological age is a metric that scientists use to predict health risks, the relevance of which can be enhanced by combining different markers. Particularly important markers are frailty and the epigenetic clock (4).

In humans, aging represents the accumulation of changes in a human being over time. There are some theories that explain this process. Biological theories of aging in humans fall into two main categories: programmed aging theories and damage theories. The programmed aging theories imply that aging follows a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. The damage theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging.

People grow old at vastly different rates, but the underlying drivers of aging likely remain the same. Ageing begins even before a baby's birth! The level of oxygen the women exposed to during their pregnancy - because of smoking, using old cooking devices, using timber and cow dung cakes for cooking, pollution, living at higher altitudes where oxygen levels will be low - dictate the rate at which their offspring age as adult. A recent study at Duke University, analyzed the health of nearly one thousand 38-year-olds and found that some resembled people a decade older while others appeared years younger. Researchers determined this “biological age” based on health indicators such as body mass index, blood pressure and cholesterol level. The finding tapped into a mystery that has long captivated scientists and the public alike — why some people can live to 120 with no disease, and others are already in bad shape at age 60.

A handful of recent studies have offered some tantalizing clues. Molecular mayhem within cells, scientists suggested this year, may lie at the root of aging. After examining populations of proteins in the brains and livers of rats, Hetzer and colleagues reported in Cell Systems that long-lived brain proteins appear to become damaged over time. “These are proteins involved in essential cellular functions,” Hetzer says. Unlike liver cells, brain cells rely on proteins that can survive for an animal’s lifetime. Some of those proteins help control messages that pass between brain cells, for example, while others help keep the cell organized. The breakdown of these proteins could be a key driver of aging, Hetzer says.

As could the unraveling of cells’ DNA, another study suggested. In healthy young people, long stretches of DNA pack tightly together in neat bundles called heterochromatin. These bundles aren’t packaged quite so well in old people, researchers comparing DNA from the teeth of young and old people found. The researchers originally identified the disorganization of DNA bundles in people with a premature-aging disorder known as Werner syndrome. The change in the 3-D architecture of the genome gives proteins easy access to stretches of DNA that are supposed to be tucked away.
Beyond the deterioration of proteins and DNA packaging, the body may age when essential barriers break down. When young stem cells in the brain divide, they build a wall that sequesters junky proteins into daughter cells. (This junk mucks with cellular machinery, a problem for stem cells churning out new brain cells.) But old stem cells aren’t so tidy, scientists reported this year in Science. Old stem cells in the brain had worn-out walls inside an organelle called the endoplasmic reticulum. These weakened walls let cellular junk seep back in during division, cutting down on the stem cells’ ability to produce new cells.

Another protective wall, the blood-brain barrier, might also waste away with time. Usually this barrier guards the brain from dangerous toxins in the blood. But MRI scans measuring barrier permeability in living human brains found that old people had leaky walls around the hippocampus, a structure involved in learning and memory. Researchers linked the leaky walls to damage to pericytes, cells found within the blood-brain barrier and crucial to its formation.

Differences in barrier integrity also showed up among old people. Those with learning and memory problems had more pericyte damage than healthy individuals of the same age, Berislav Zlokovic of the University of Southern California in Los Angeles and colleagues reported in Neuron. Breakdown of this brain barrier may kick off some of the cognitive troubles of old age, the authors proposed.

All in all, scientists continue to chip away at the mysteries of growing old. The molecular events identified this year add to previously discovered signs of aging — the shortening of telomeres, the protective caps on chromosomes, for example, and damage to mitochondria, the energy factories of cells. But the picture isn’t complete, or simple. Big questions remain, including how to distinguish healthy aging from disease, as well as the roles of genetics versus environment.

How shortening of telomeres cause aging: In humans and other animals, cellular senescence (to grow old) has been attributed to the shortening of telomeres (Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces) at each cell Division. When telomeres become too short, the cells die. The length of telomeres is therefore the "molecular clock". This agrees with the 'aging-clock theory' which suggests that an aging sequence is built into the operation of the nervous or endocrine system of the body. In rapidly dividing cells, shortening of the telomeres would provide such a clock. This idea is in contradiction with the evolutionary based theory of aging.

When we think of the DNA that makes up our chromosomes, we usually focus on our genes. But at the end of every chromosome in our body lies a long chain of repetitive DNA called a telomere, which acts as a protective cap. As we age, these caps get shorter. Now studies find that chronic pain and phobic anxiety are linked with shorter telomeres, which suggests that sufferers of these ailments may be aging prematurely! Time naturally shortens telomeres because whenever a cell divides, a portion of the telomere is not replicated. But telomere length can be reduced by other stressors, too, including depression, trauma andobesity. A recent Harvard University study adds anxiety to the list. People with high phobic anxiety, such as that characteristic of panic disorder and agoraphobia, had shorter telomeres, according to a paper published in PLOS ONE.

Telomeres have experimentally been shown to shorten with each successive cell division. Shortened telomeres activate a mechanism that prevents further cell multiplication. This may be particularly limiting to tissues such as bone marrow and the arterial lining where cell division occurs repeatedly throughout life. The quantity of the hematopoietic stem cells that produce the blood components residing in the bone marrow of human beings have been found to decline with aging. Stem cells regenerative capacity is affected by the age of the recipient. Importantly though, mice lacking telomerase enzyme do not show a dramatically reduced lifespan, invalidating at least simple versions of the telomere theory of aging. Laboratory mice may be an exception for the theory, as they have long hypervariable telomeres, which prolong the period after which telomere shortening would affect life-span. However, wild mouse strains do not, and telomere length in these breeds is unrelated to lifespan.

Shortened telomeres have been observed in several types of cancer, coronary heart disease, hypertension, diabetes and arthritis. Accelerated telomere shortening can signal vulnerability to disease, premature aging or even death. In addition, participants with shorter telomeres had increased pain sensitivity and decreased gray matter volume in pain-processing areas of the brain. Fibromyalgia patients with high levels of both depression and pain had telomeres that looked approximately six years older than those of patients who had lower levels of depression and pain. 

Researchers are also finding that your mental patterns and thoughts could be harming your telomeres — essential parts of the cell’s DNA — and affecting your life and health(1). People who score high on measures of cynical hostility have shorter telomeres. When you ruminate, stress sticks around in the body long after the reason for the stress is over. Another culprit is thought suppression, the attempt to push away unwanted thoughts and feelings. Ironic error may also be harmful to telomeres. If we try to manage stressful thoughts by sinking the bad thoughts into the deepest waters of our subconscious, it can backfire. The chronically stressed brain’s resources are already taxed — we call this cognitive load — making it even harder to successfully suppress thoughts. Instead of less stress, we get more. In a small study, greater avoidance of negative feelings and thoughts was associated with shorter telomeres. 

Different organs in the same individual too can age differently. For instance, some stem cells vital to lung cell oxygenation undergo premature aging — and stop dividing and proliferating — when their telomeres are defective. The stem cells are those in the alveoli, the tiny air exchange sacs where blood takes up oxygen. In studies of these isolated stem cells and in mice, Armanios’ team discovered that dormant or senescent stem cells send out signals that recruit immune molecules to the lungs and cause the severe inflammation that is also a hallmark of emphysema and related lung diseases.

Another internal process experts use to define human’s biological age is methylation of DNA. As the journal Nature defined, methylation “is a common epigenetic signaling tool that cells use to lock genes in the ‘off’ position.” Researchers added the active role of methylation is unknown, “but it appears that proper DNA methylation is essential for cell differentiation and embryonic development.” This explains how cells that are coded the same — see heart and brain cells — can function differently. If every cell in the human body contains the same DNA sequence, how does a heart cell differ from a brain cell? The answer lies within epigenomics.

The study of epigenomics is the study of a cell’s changes in genetic material. A combined set of these changes are known as an epigenome and they alter cell expression, not DNA sequence. So you don’t have to change the DNA itself in order to change how cells are expressed.

An epigenome is what ensures a heart cell is different from a brain cell in spite of the fact they’re coded the same; it’s as flexible as it is complex. Leading science journal Nature (that is behind the video below) reported a much talked about change stems from DNA methylation. This occurs when a chemical is added to DNA and primes the gene to turn off. Aging accounts for cell change, too. For example, Nature reported an increase in methylation in older brains. Varied eating, smoking, and exercise habits have also been found to influence cells. And a disease like cancer can cause cells to "replicate out of control."

DNA methylation is a mechanism used by cells to control gene expression—whether (and when) a gene is turned on or off. This differs across cells and tissues and has been shown to change gradually as we age. The level of methylation can therefore help determine tissue age.

By charting how age affects DNA methylation levels throughout life, scientists have created an epigenetic clock. This is a widely used method for determining biological age from a DNA methylation sample based on hundreds of epigenetic markers. But  new research, published in Genome Biology, suggests the method isn't as reliable as previously thought (2).

The most commonly used version of the clock was originally developed from a large collection of data taken from a range of different tissue types.

Where tissue samples come from anonymous donors, the epigenetic clock allows researchers to estimate their chronological age, give or take a few years. By focusing on biological age, it's been proposed that the epigenetic clock reflects our "true" cellular age. This may be altered by our health or the environment we live in. 

Many studies have explored age acceleration—how our clocks might be sped up by illness or the environment, and even how this might relate to the risk of death. In essence, this calculates the difference between chronological and biological age for a set of people. You then take this difference and test whether it correlates with the profile of people suffering from a certain disease.

This possibly allows researchers to look at developmental changes, cumulative environmental effects and cellular aging. But there has also been hype surrounding it.

It's important to remember that there's no evidence that the DNA methylation changes used in the epigenetic clock are anything more than a by-product of aging. In fact, they may not determine our aging.

The original samples used in developing the clock model were predominantly taken from younger people and didn't include many from elderly people. Given what we already know about the biological changes that take place as we age, we wanted to test the clock's accuracy, particularly at the older end of the age spectrum.

Age acceleration studies must take account of this, otherwise they risk being fooled by any age-related phenomenon looking like it is associated with DNA methylation.

By looking at data on elderly people from two large studies, one performed in about 90 elderly postmortem brains and the other in bloods from nearly 1,200 people of all ages, we could compare two epigenetic clock models against our DNA methylation results.

Our analysis of the performance of the clock shows that epigenetic age doesn't move at a steady pace throughout life, and that it performs differently in different tissues. Instead, the clock slows as we age, particularly as we enter old age.

We found clear evidence that the ages of people were systematically underestimated by the epigenetic clock, once people were over the age of about 60. At the moment, we don't know why DNA methylation change slows down in this way, or what mechanisms are behind it.

We already knew that DNA methylation changes are not linear over the lifespan. The clock has been updated to account for the big changes taking place in childhood and adolescence, for example. With the amount of data now available, more detailed and accurate clocks for specific tissues and age ranges are possible.

The epigenetic clock is a useful tool for researchers, but given the limited nature of the DNA methylation profile that the clock is based on, taking it at face value could lead to misleading results(3).

Genetic ties to lifespan: A variation in the gene FOXO3A is known to have a positive effect on the life expectancy of humans, and is found much more often in people living to 100 and beyond - moreover, this appears to be true worldwide. FOXO3A acts on the sirtuin family of genes which have also been shown to have a significant effect on lifespan, in yeast and in nematodes (round worms). Over-expression of the RAS2 gene increases lifespan in yeast by 30%.

How calorie intake effects aging: Diet (specifically, caloric restriction) has been shown to substantially affect lifespan in many animals, including the delay or prevention of many age-related diseases. Typically, this involves caloric intake of 60–70% of what an ad libitum ( refer to the "free-feeding" weight of an animal, as opposed, for example, to the weight after a restricted diet) animal would consume, while still maintaining proper nutrient intake.

Some studies have shown that highly reactive free radicals ( Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed these radicals can start a chain reaction, like dominoes.  Generally, free radicals attack the nearest stable molecule, "stealing" its electron. When the "attacked" molecule loses its electron, it becomes a free radical itself, beginning a chain reaction. Once the process is started, it can cascade, finally resulting in the disruption of a living cell) arise normally during metabolism. Sometimes the body's immune system's cells purposefully create them to neutralize viruses and bacteria. However, environmental factors such as pollution, radiation, cigarette smoke and herbicides can also spawn free radicals.

Normally, the body can handle free radicals, but if antioxidants are unavailable, or if the free-radical production becomes excessive, damage can occur. Of particular importance is that free radical damage accumulates with age.  The biological theory of aging that points to a buildup in cells of waste products that presumably interfere with metabolism. Evidence supporting this theory is the presence of a waste product called lipofuscin leading to age pigment. Lipofuscin is formed by a complex reaction that binds fat in the cells to proteins. This waste accumulates in the cells as small granules and increases in size as a person ages.

This damage to cells can be restricted through  less metabolic processes through dieting. That is where low calorie intake helps.

Inflammation is your immune system's reaction to irritation, injury, or infection. It's a normal response (and actually a good thing) and it's a natural part of healing. But, it's possible that chronic inflammation could have a negative impact on your body and your health.

Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process. The Role of Inflammation in Age-Related Disease and also in the biological aging process is well documented. For many, inflammation is simply understood as a trajectory of biomarkers, for example the appearance of IL-6 or C-reactive protein (CRP), associated with a disease. However, inflammation is a very complex response to an injury, infection, or other stimulus, in which many different cells types and secreted factors orchestrate protective immunity, tissue repair, and resolution of tissue damage. Whereas acute inflammation limits tissue damage and resolves, chronic prolongation of the inflammatory state leads to progressive tissue damage. The mild pro-inflammatory state of aging is dangerous. Among the causal pathways linked to the major diseases associated with aging, including physical frailty, are changes in body composition, energy imbalance, homeostatic dysregulation, and neurodegeneration. Chronic inflammation is strongly connected with each of these aging phenotypes. Inflammation blocks critical metabolic signals that support muscle maintenance. Skeletal and muscle working conditions, degeneration and regeneration of damaged tissues are determined by inflammation. This in turn causes slow walking and low cognitive speeds.

mTOR,  a protein that inhibits autophagy ( the natural, destructive mechanism that disassembles, through a regulated process, unnecessary or dysfunctional cellular components)  has been linked to ageing through the insulin signalling pathway. It has been found, in various model species, that caloric restriction leads to longer lifespans, an effect that is likely mediated by the nutrient-sensing function of the mTOR pathway. mTOR functions through nutrient and growth cues leading scientists to believe that dietary restriction and mTOR are related in terms of longevity. When organisms restrict their diet, mTOR activity is reduced, which allows an increased level of autophagy. This recycles old or damaged cell parts, which increases longevity and decreases the chances of being obese. This is thought to prevent spikes of glucose concentration in the blood, leading to reduced insulin signalling. This has been linked to less mTOR activation as well. Therefore, longevity has been connected to caloric restriction and insulin sensitivity inhibiting mTOR, which in turns allows autophagy to occur more frequently. It may be that mTOR inhibition and autophagy reduce the effects of reactive oxygen species (chemically reactive molecules containing oxygen) on the body, which damage DNA and other organic material, so longevity would be increased.

Life-span is selected. Traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death. Such a genetic effect is called the antagonistic pleiotropy  (the phenomenon where one gene controls for more than one phenotypic trait in an organism. Antagonistic pleiotropy is when one gene controls for more than one trait where at least one of these traits is beneficial to the organism's fitness and at least one is detrimental to the organism's fitness) effect when referring to a gene (pleiotropy signifying the gene has a double function - enabling reproduction at a young age but costing the organism life expectancy in old age) and is called the disposable soma ( presumes that the body must budget the amount of energy available to it) effect when referring to an entire genetic programme (the organism diverting limited resources from maintenance to reproduction). Some of the genetic variants that increase fertility in the young are now known to increase cancer risk in the old. Such genes include p53 and BRCA1. The biological mechanisms which regulate lifespan evolved several hundred million years ago.

According to reproductive cell theory the idea that aging is regulated by reproductive hormones that act in an antagonistic pleiotropic manner via cell cycle signalling, promoting growth and development early in life to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and lead cells to aging.

Autoimmune theory says that the idea that ageing results from an increase in autoantibodies  {an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins} that attack the body's tissues. A number of diseases associated with aging are  autoimmune in this way. While inflammation is very much evident in old mammals, even severe combined immunodeficiency, SCID ( a genetic disorder characterized by the disturbed development of functional T cells and B cells of the immune system caused by numerous genetic mutations that result in heterogeneous clinical presentations) mice in SPF colonies still experience senescence ( getting old).

Genetic damage has two types. Mutations are damages to the DNA sequence, while epimutation is damage to the DNA scaffolding which regulates gene expression in the cell. Both ultimately harm our health by causing abnormal gene expression. Some (epi-)mutations lead to cancers, which are the uncontrolled growth and division of cells.

Gene loss theory of ageing: It has been established that humans lose approximately 0.6% of the DNA in their heart muscle cells annually.  Yearly DNA loss in the brain and lymphocytes also happens with such a percentage.  This is almost certainly (or probably the) central cause of aging.

Moreover,  ageing results from chance events that escape proof reading mechanisms, which gradually damages the genetic code. As we age, more and more errors accumulate in the code because of the division of cells throughout our lives. Misrepairs that cannot correct the errors lead to damage of cells.

Premature aging is a consequence of mis-construction of tissues and organs during development, which is caused by genetic disorders. The abnormality of tissue structure is the common point between premature aging and normal aging, and it links a defective development and a defective repair.

A person's biological age is a better measure for determining a person's health than is chronological age. The former is more closely tied to one's risk of age-related diseases, such as dementia and osteoporosis, than was one's chronological age. Therefore, all the 20year old people are not the same and so are all 60 or 100 year old human beings.
Next time you blame somebody for his or her general health think of all these factors to determine their biological age and try to understand how their bodies are operating and coping with all these factors! And please don't ridicule people for what they are and things that are not in their control.
And need I add - taking only chronological age into consideration while issuing insurance policies and selecting candidates for jobs is out of date now?

Citations:

1. http://ideas.ted.com/could-your-thoughts-make-you-age-faster/

2. https://sciencex.com/news/2020-01-aging-epigenetic-clocks-older.htm...

3.  Louis Y. El Khoury et al. Systematic underestimation of the epigenetic clock and age acceleration in older subjects, Genome Biology (2019). DOI: 10.1186/s13059-019-1810-4

4. https://medicalxpress.com/news/2020-02-biological-age-health.html?u...

Updates:

Difference between retina's biological age and person's real age linked to heightened death risk

The difference between the biological age of the retina, the light sensitive layers of nerve tissue at the back of the eye, and a person's real (chronological) age, is linked to their risk of death, finds research published online in the British Journal of Ophthalmology.

This 'retinal age gap' could be used as a screening tool, suggest the researchers.

A growing body of evidence suggests that the network of small vessels (microvasculature) in the retina might be a reliable indicator of the overall health of the body's circulatory system and the brain.

While the risks of illness and death increase with age, it's clear that these risks vary considerably among people of the same age, implying that 'biological aging' is unique to the individual and may be a better indicator of current and future health, say the researchers.

Several tissue, cell, chemical, and imaging-based indicators have been developed to pick up biological aging that is out of step with chronological aging. But these techniques are fraught with ethical/privacy issues as well as often being invasive, expensive, and time consuming, say the researchers.

They therefore turned to deep learning to see if it might accurately predict a person's retinal age from images of the fundus, the internal back surface of the eye, and to see whether any difference between this and a person's real age, referred to as the 'retinal age gap', might be linked to a heightened risk of death.

Deep learning is a type of machine learning and artificial intelligence (AI) that imitates the way people acquire certain types of knowledge. But unlike classic machine learning algorithms that are linear, deep learning algorithms are stacked in a hierarchy of increasing complexity.

The researchers drew on 80,169 fundus images taken from 46,969 adults aged 40 to 69, all of whom were part of the UK Biobank, a large, population-based study of more than half a million middle aged and older UK residents.

Some 19,200 fundus images from the right eyes of 11,052 participants in relatively good health at the initial Biobank health check were used to validate the accuracy of the deep learning model for retinal age prediction.

This showed a strong association between predicted retinal age and real age, with an overall accuracy to within 3.5 years.