The science and art of aging

“As a species we accept our inevitable decay decline and death; I want to argue that the opposite should be true.”

– Bryan Johnson, bio hacker, founder, Project Blueprint.

Humans, with their infinite capacity for overreaching, have always pursued the elusive goal of defying death. It is no surprise then, that myths, crafted as ideals to aspire to, across nations and cultures have been built, positing death defying and eternal youth as within the realm of the possible. If in Indian Hinduism, it is the legend of Amrit, or the nectar of immortality, which is said to grant eternal life to whoever drinks it, Arthurian legend glorifies the Holy Grail as a chalice with miraculous healing powers, capable of granting eternal youth or sustenance in infinite abundance. Even at its minimum, human endeavour has always been to live disease-free, and healthy; the extension of life years is a bonus that was not sought, but taken with varying degrees of gratitude.

Through history, philosophers have propounded views that see-sawed between Plato’s belief in death as liberation of the soul, through the medieval conviction in Christian theological proposition of being welcomed into the kingdom of God after death, and to the existentialist position that rendered absurd both death and life. Questions of life, death and ageing have always been at the centre of humanity’s curiosity and cogitation. While men and women remain fully cognisant of death as an endpoint, at least in the earthly realm, it is their faith, or reason, that guides their belief on what happens after. As the Gregorian chant used in elegiac liturgy from the 9th century goes: “In the midst of life, we are in death.” Oftentimes, the reassurance of religion, of a better life after death too, has not restrained even the faithful from looking towards a longer life on earth, prolonging life to as long as it is scientifically possible. If there is no debility or disease, this urge to prolong life beats in time with a healthy heart.

A few definitions

Any talk of life and longevity is thus rooted in death and ageing. But age and ageing are different things, though often conflated together. As the Max Planck Institute for Biology of Ageing is quick to remind us, “age is just a number and is often subjective. Ageing, on the other hand, is an observable process that can be described and defined scientifically.” An article by Lopez-Otin et al, published in the peer-reviewed journal Cell, in 2013, attempts to define the ‘hallmarks of ageing’. “Ageing is characterised by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases,” it says.

No one contests that ageing is a completely normal occurrence. But did you know that some experts believe that it begins from the age of 20, and there are others, who are convinced that it begins before birth, while yet others lay it at the stage of sexual maturity? The long-held view, however, is that, as the Max Planck Institute website says, many classic signs of ageing can become apparent in the human body after 20 years. Wrinkles appear as the skin loses elasticity due to the loss of collagen, elastin and hyaluronic acid. Endurance decreases and the number of hair cells in the cochlea decreases, making it harder to hear high-pitched sounds. By the age of 25, fertility in women and testosterone levels in men start to decline; a little later, sperm density also decreases in men. From the age of 30, the elasticity of the cartilage slowly decreases and certain movements become more difficult. The intervertebral discs also become thinner. From the age of 35, the first grey hairs begin to appear as melanin production slows down and later stops altogether. Around the age of 40, the lens of the eye thickens and loses its flexibility (presbyopia) and reading becomes more difficult.

“From the age of 55, muscle loss increases and the body changes its ratio of muscle to fat. The ageing process begins to show in the calcification of the blood vessels, causing blood pressure to rise. Organs such as the kidneys and liver begin to function less efficiently, which means that the body’s detoxification process slows down. As we age, neurodegenerative diseases such as dementia (e.g. Alzheimer’s), Parkinson’s, cardiovascular disease and cancer become more common, to name just a few of the most common age-related diseases,” the Institute’s website details.

There are a few more definitions that are of relevance here, and let’s get that out of the way first. Life expectancy is basically the average lifespan of a population, while maximum lifespan is the maximum time that one or more members of a population have been observed to survive between birth and death. The recorded oldest woman in the world, Jeanne Calment, lived to over 122 years old, so the maximum human lifespan is often pegged at 120 years.

The term longevity, on the other hand, describes the ability to live a long life beyond the species-specific average age at death. Longevity can be considered as the average lifespan under ideal conditions, the Max Planck Institute says. Additionally, the term healthspan describes the period of time during which a person is healthy within his or her lifespan.

In March 2022, the government honoured Indian yoga guru based in Varanasi, Swami Sivananda who claims to have been born in 1896, with the Padmashri. As per his claim, he is the oldest man living in India, at 128 years, still mobile and able to teach yoga.

Ageing research has, over the years, advanced phenomenally, with funding constraints disappearing as ostensible milestones are crossed. As Lopez-Otin et al say, in their paper: there has been “unprecedented advance over recent years, particularly with the discovery that the rate of ageing is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution.” Consequently, over the years, super centenarians have been lauded and their lives chronicled, most of them regaling audiences with tales of how they lived not necessarily healthily, but by and large, did what they pleased.

The hallmarks of ageing

What are the molecular and cellular hallmarks of ageing? The Max Planck Institute has an elaborate list. Genomic instability is at the top of that list. The human DNA is constantly being damaged by external and internal factors (including UV radiation from sunlight), up to an estimated a million times a day. Most of this damage is repaired immediately because cells have efficient detection and repair mechanisms. However, these repair processes are not perfect and a small percentage of damage remains unrepaired. DNA damage accumulates as one ages, and these can have several adverse effects, including the risk of tumour growth.

Telomere degradation also is a key marker. Telomeres are the protective caps at the ends of the chromosomes in the human genome. Each time a cell divides, a piece of telomere is lost, so the more cells divide and the older we get, the shorter the chromosome ends become. When a certain length is reached, cells enter a resting phase and stop dividing. Changes in the epigenome have a definite impact. The information in the DNA is not only stored in the base pairs, but also in chemical modifications to these letters, known as epigenome. Unlike the genetically encoded information, which is very stable, the epigenome is very dynamic and changes in response to diet, drugs or stress, and age.

With advancing age, there is also loss of proteostasis, or the ability of proteins to remain in good condition and allow cells to function properly. Stress or the accumulation of damage over time can cause cells to enter a state called cellular senescence, where they stop dividing, lose their original function and begin to release harmful molecules.

Dysfunction of the mitochondria, known as the powerhouse of the cell, the depletion of stem cells or their ability to repair organ damage, and altered intercellular communication have also been listed under markers. Ageing is characterised by an increase in inflammation, and the diversity of the gut microbiome decreases with age, and in older people contains more pathogenic bacteria that cause disease.

A mix of genes and lifestyle factors

So, is there a guarantee for longevity? Does one get lucky with one’s genetic load, or do one’s lifestyle choices make a difference? Is it a healthy lifestyle, or is it the genes one inherits? This question is not so easily answered, it turns out. As De benedictis and Franceschi, claim in their 2006 paper in Science of Aging Knowledge Environment: “In no species other than humans do cultural, social, and biological factors interact with each other in modulating complex phenotypes. Thus, the identification of genetic factors that affect human longevity is a true challenge.”

Undeniably, there are people who have hit the jackpot as far as genes go, and have inherited a long, healthy life, one that takes them well beyond the average life expectancy. Life expectancy in nations across the world has been increasing steadily over the years, what with advances in liveability, standards of care, and advances in medical technology. From a life expectancy of 46.4 years (both sexes) in 1950, the average life expectancy globally has increased to 73.3 in 2024, as per the United Nations Population division estimates. In India, it was 41.2 (both sexes) in 1950 and increased to 72.2 in 2024.

Chandrakanth Lahariya, primary care physician, academician and health policy researcher, takes a broad-based view and says a mere medical science perspective on this would be poor and insufficient. Pointing to the lessons from David S. Landes’ book, The Wealth and Poverty of Nations, he says, the reasons for improved age expectancy arise from a complex mesh of sociological and medical factors. For instance, much of the improved life expectancy of most nations (before the antibiotic era) had come from improved sanitation. Income growth was also rendered possible because of this. The second major period of improvement relates to the development of antibiotics and vaccines, and thirdly, the bettering of newborn and infant survival has been crucial in determining adult survival. “We have, globally, improved maternal and child mortality. Increased life expectancy has also emerged as consequence of population control activities,” says Dr. Lahariya.

Clearly, population-level improvements in life expectancy that are evident today have roots in factors beyond genes, and in factors that have to do with lifestyle choices or compulsions that expose people to disease, or ensure their health. There is sufficient evidence that adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy, as per a study on adults in the United States adults. In ‘Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population’ in the journal Circulation, Yanping Li et al argue that adherence to five low-risk lifestyle-related factors (never smoking, a healthy weight, regular physical activity, a healthy diet, and moderate alcohol consumption) could prolong life expectancy at age 50 years by 14.0 and 12.2 years for female and male US adults compared with individuals who adopted zero low-risk lifestyle factors.

The Indian Study of Healthy Ageing, a study of approximately 2,20,000 individuals aged 30-69 in Maharashtra, was set up jointly by Oxford Population Health and The Centre for Cancer Epidemiology, Tata Memorial Hospital, Mumbai, with the aim of examining environmental and genetic causes of cancer and other non-communicable diseases in a population with a low baseline risk. The study also seeks to understand the relevance for disease risks of India’s recent and ongoing transitions in major lifestyle factors. As India is going through a major transition in lifestyle behaviours, also spilling into rural areas, the study, which will publish data by 2026, will help understand the impact of these changes on the health of the population and mortality, researchers say.

Many studies have stressed on the beneficial effect that dietary restriction, without malnutrition, has on positive ageing. A 2015 paper by Fontana and Partridge in Cell, showed that reduced food intake, and avoiding malnutrition, can ameliorate ageing and ageing-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Micronutrient deficiency, on the other hand, can have a negative impact on health, affecting senior citizens more acutely.

Senior geriatrician V. S. Natarajan, often referred to as the father of geriatric medicine in India for his contribution towards establishing geriatrics as a medical speciality in the country, says, much today depends on lifestyle factors: a combination of diet, meditation and exercise. “The thing, though, is that you have to put all this in place when you are 35 or 40 years old, in order to reap the full benefits. Most people start too late.” He delineates the normal ageing process from unhealthy ageing. “What is the natural, normal ageing process? It’s where you might develop cataract, lose some hearing, experience greying of the hair, receding of the hairline, and constipation, maybe. These can be easily addressed or managed and do not affect quality of life too much.” His emphasis on adult vaccination stems from his experience in the initial decades of his career, where mortality was primarily due to infectious diseases. That has changed now, shifted track to non-communicable diseases, he adds, making the recommendation of initiating healthy lifestyle choices early very significant.

Charting Blue Zones

Studying Blue Zones around the world gives us a hint that the secret to a long healthy life is not vested in genes alone. Blue Zones are regions where people live significantly longer and healthier lives compared to the global average. These areas were identified by researcher Dan Buettner in collaboration with National Geographic and other scientists studying longevity. People in Blue Zones often live to be 90 or even 100-plus years old while maintaining good health and avoiding many chronic diseases. The five official blue zones are: Okinawa in Japan; Sardinia in Italy; Nicoya Peninsula in Costa Rica; Ikaria in Greece; and Loma Linda in California. Researchers have recorded certain factors that influence longevity in these areas: following a plant-based diet including vegetables, legumes, and whole grains, consuming little or no processed foods and sugars, and moderate alcohol, undertaking regular physical activity, forming and retaining strong social connections, maintaining low stress levels, and demonstrating a strong sense of purpose or will to live.

Studies have shown that people in Blue Zones also experience significantly lower rates of dementia than populations in industrialised nations like the U.S. and Europe;, slower cognitive decline in older age, and a lower prevalence of Alzheimer’s disease, particularly in places such as Ikaria, Greece, where dementia is almost non-existent.

Cognitive health

Prolonging cognitive health is a real thing, chimes in E.S. Krishnamoorthy, neuropsychiatrist and founder, Buddhi Clinic, a centre that focuses on going beyond medication, to integrating modern science and ancient wisdom, to offer individuals care and rehabilitation. He introduces the concept of synaptic plasticity — the ability of synapses (the connections between neurons) to strengthen or weaken over time in response to activity, experience, or environmental changes. It is a fundamental mechanism underlying learning, memory, and neural adaptation. “When we do things that promote it – for instance learn a new language or a new skill, we are enhancing cognitive ability. The strongest evidence is for language and verbal felicity, which is why doing crosswords or word games or Sudoku is being encouraged,” he says.

As in the Blue Zone areas, he adds that socialisation is also an important tool — lonely people age cognitively faster. Again, lifestyle factors also have a role to play – insulin resistance, exercise and diet. The recommendation today is to continue with what is closest to your own genetic experience. Straying far away from this genetic experience, for instance, in terms of diets, might be inimical to intended progress. To illustrate, he says: “The Mediterranean diet might be a fad, but you must realise that it comes with a set of factors – people there, eat in the sun, with company, and over hours. That is what works, as a whole. Going very far away from native habits and practices may also impact negatively on the gut microbiome, which we know today, has an impact on brain health as well.”

While there is a natural decline of hours and quality of sleep with old age, Dr. Krishnamoorthy says he is not so concerned about this process. “All the damage happens in middle age, when we are scurrying about, trying to build careers and grow professionally. “We need sleep to clear the wastes from our brain, and sleeping also promotes synaptic plasticity.”

Bio hackers

In recent years, biohacking has emerged as a trend on the far end of the spectrum that addresses ageing. Biohacking is the practice of making small, incremental changes to one’s body, mind, or lifestyle to enhance performance, health, and well-being. Biohackers have added a wide range of activities to their daily routine, from simple lifestyle changes to advanced, intrusive, scientific experimentation. Among the more prominent biohackers are Dave Asprey, Ben Greenfield, Bryan Johnson, Tim Ferriss, Elizabeth Parrish and Josiah Zayner, some of them more radical and hardcore in the changes they have made, than others.

The age-defying journey of the wealthy entrepreneur and founder of Project Blueprint, Bryan Johnson, is the subject of the Netflix documentary Don’t Die: The Man That Wants To Live Forever. In it, Johnson swears that human beings have the “ability to stop their self-destructive behaviour and neutralise ageing”. He also boasts that he has reversed his biological age by 5.1 years, and that he ages only eight months in a year. Some of Johnson’s recommendations make sense, and fall within the larger gamut of pursing a healthy lifestyle — exercising for an hour every day regularly, focusing on a nutrient-dense, plant-based diet, sleeping early and a full eight hours every night.

But some things are definitely extreme, and quite impossible for others to follow: for instance, he says he eats his last meal of the day at 11 a.m., claiming that completing the digestion process well before his bedtime helps him maintain a low heart resting rate and ensures better quality of sleep. He reportedly underwent a series of six-monthly 1-litre plasma transfusions, but discontinued these due to a lack of observed benefits. In the documentary, he numbers the pills (over 100) he takes daily, including vitamins, minerals and other experimental compounds. In an effort to restore youthful facial volume, Johnson underwent ‘Project Baby Face’ to inject donor fat into his face, an experiment he documented on YouTube. This procedure led to a severe allergic reaction, causing significant facial swelling, but that did not prevent him from marching on on his quest to live forever, aided by his nearly bottomless wealth.

Biohacking is not for all, neither is immortality. But healthy ageing is well within the grasp of human beings today. To seize it, and hold on to it, with some well-made life choices should be the goal. The Holy Grail, today, is a secret that nestles within, but the journey to arrive at the right formula might well be a task, demanding, as it does, inclination and endurance, even sufferance in equal measure.