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The science of growing old and older

From Kaya Kalp in Ayurveda to the latest genetic technology, the fastest-growing science in the world is anti-aging.

Published: 10th October 2021 05:00 AM  |   Last Updated: 09th October 2021 11:33 AM   |  A+A-

Creating a healthy long-living young person is the Holy Grail of biotechnology. And it doesn’t come cheap.

Creating a healthy long-living young person is the Holy Grail of biotechnology. And it doesn’t come cheap. (Representational image)

The gods do not grow old. They live in human imagination as luminous forms of splendour, ever-youthful and glowing, exactly as they are in mythological stories and calendar illustrations. But men and women who worship them do age, even as some strive to be gods themselves. For millennia, mankind, obsessed with the divine and immortality, has been struggling to find ways and means to live longer—‘may you live long’ is an ancient blessing, or a curse depending upon the time, place and situation.

From Kaya Kalp in Ayurveda to the latest genetic technology, the fastest-growing science in the world is anti-ageing. The first Longevity Economy report released in 2013 by AARP and Oxford Economics calculated that the Longevity Economy was worth $7.1 trillion in annual economic activity. This figure has been revised up to $7.6 trillion. British biomedical gerontologist Aubrey de Grey who claims to be “spearheading the global crusade against ageing” predicts that by 2023, people who can afford therapies like making molecules younger won’t be affected by aging-related diseases entirely. 

Biogerontologists at Sierra Sciences are working to lengthen telomeres, the “caps” at the end of each strand of DNA, which get shorter every time a cell divides itself. After a well past middle age, the cells become inactive, as the telomeres get very short. Putting the telomeres in reverse gear to their state at your birth is posited to reduce your biological age to 25, not like the world according to Garp, but the age when maturity begins to arrive. The CEO of Sierra Sciences competitor Bio Viva, Elizabeth Parrish, underwent telomere therapy in 2015 and found that her telomeres had “grown younger” by roughly 30 years, causing her body to reverse age.

Setting the Age Bar: The uniqueness of such experiments apart, human life is just a wrinkle in the great topsail of time. But the global anti-ageing services market size, estimated at $24.6 billion in 2019, was expected to reach $25.9 billion before the pandemic. Science isn’t giving up. A Bank of America report predicts that the market will expand to $610 billion by 2025, from the currently estimated $110 billion. In secret government-financed facilities, university research centres and corporate-funded labs, the search has moved on from extending life to reversing ageing.

Findings of research published in May in the respected science journal Nature Communications reveal that humans can live up to somewhere between 120 and 150 years. The spirit of science is as much contradiction as it is discovery. In 2018, a study published in its prestigious rival, Science magazine, concluded that the chance of people dying rose when they neared 80, but slowed and plateaued at around 105, giving them a 50 per cent chance of reaching next year. The same was true at 106, 107, 108, and 109. The findings “strongly suggest that longevity is continuing to increase over time, and that a limit, if any, has not been reached.”

Creating a healthy long-living young person is the Holy Grail of biotechnology. And it doesn’t come cheap. For example, Libella Gene Therapeutics charges $1 million to reverse what it claims ageing by up to 20 years. Dr Keshav K Singh, Scientific Founder and Chief Scientific Officer of US-based Yuva Biosciences, and Director of Cancer Genetics at the University of Alabama, Birmingham, US, believes that the cost attached to procedures and price of drugs will come down with ongoing research. “Since there is a huge market, prices will come down eventually. Also, India needs to develop infrastructure and expand research on ageing,” he says.

Many life-extending products and procedures are being discovered, but most of them haven’t been tested on humans. The pill 516 can get you a fit body without a single pushup—it tricks the brain into believing muscle has been exercised daily. It works by reprogramming the muscles and increases endurance by 70 per cent. Another tablet named Compound 14 deceives the body’s fat burning system into believing that the cells have depleted all their energy; it is still in animal trial stage.

At Northwestern University in the US, scientists managed to turn off the “genetic switch” that causes ageing in worms. American researchers revived old mice by infusing blood from young mice and believe the procedure will be successful in humans in three to five years. Scientists at the MDI Biological Laboratory, in collaboration with colleagues from the Buck Institute for Research on Aging in Novato, California, and Nanjing University in China, have identified synergistic cellular pathways that can increase lifespan five times—the equivalent of a human living for 400 or 500 years.

Age in the Cells: Famous British biogerontologist Andrew Steele lays down three hallmarks as 
the root causes of ageing:

1. Genomic instability: Our genes get damaged as we age. If this can be stopped, the ageing process will slow down. 

2. Cellular senescence: An ageing body accumulates senescent cells—an ageing non-cell that stops replicating it doesn’t die, accumulating within the body and causing serious diseases like age-related cancer.

3. Mitochondrial dysfunction: Our cells get their energy from mitochondria, which generate the energy that powers cells. Mitochondrial dysfunction speeds up ageing.

A few years ago, hitting the 90s was as rare as an old man skydiving. Until the last century, a poor Indian was lucky to reach 30. China and India have caught up with Western nations—our average life expectancy is around 70 years now. “The current life expectancy for India in 2021 is 69.96 years, a 0.33 percent increase from 2020. One of the big reasons for this is technological, surgical and cosmetic advancements, as well as an exponential growth in the health and fitness industry. The intake of nutritional supplements has also grown steadily in India. The Indian dietary supplement market, valued $3,924.44 million in FY2020, is predicted to grow at CAGR of 17.28 percent until FY2026, to reach $10,198.57 million,” says Avni Kaul, Nutritionist and Wellness Coach and Founder, Nutri Activania. 

The UN estimates that the number of centenarians on earth will rise to 3.7 million by 2025 from around 600,000 today. The math has method. From age zero to 21 meant living about 8,000 days. From 21 to midlife is another 8,000 days. From the mid-40s to 65 is again 8,000 days. With doctors giving a 50-50 chance for a 65-year-old person to live to 85, it is another 8,000 days. British Nobel laureate Peter Medawar proposed that the reason for ageing is decay in cellular replication after reaching reproducing age. Considering the theory that the purpose of evolution is reproduction and propagation of the species, cells without reward make mistakes while copying DNA, causing mutations. 
 
The Time of the Lookist: As the world gets richer and urban medical systems become more sophisticated, pushing back the biological clock is an international obsession, not just with the wealthy but also the well-heeled middle classes. To be a lookist is to be a realist—cosmetics come first in the race for eternal youth. There is hardly an actor or public figure who hasn’t gone under the knife or doesn’t use youth boosting products. “A decade or two back, hardly anyone thought of reversing age or going under the knife to look young. But now this segment is flourishing. And the first aspect is looks where the market is flooded with products that promise anti-ageing properties and also cosmetic procedures to make you look young,” says Dr Syed Nazim Hussain, Aesthetic Surgeon and Consultant Dermatologist, Max Hospital, Gurgaon, who has treated several 70-year-olds for wrinkles in the last two years. 

Technology and business call the shots since companies dealing in anti-ageing sciences are mopping up investors. In 2018, Google launched its new medical company Calico, whose mandate is to counter physical ageing. It claims that by 2029, an extra year would be tacked on every year to people’s life expectancy. Products and drugs are available on the market since decades, which claim to make you look younger, remove wrinkles and facial flaws. These do brisk business, moving up levels, competing with one another as if life itself is a beauty contest.

While quacks of antiquity advertised the elixir of youth derived from magic lizards and the nails of the True Cross, modern medical advances in vaccine research, new antibiotics and knowing what’s good for the mind and body has made massive advances in ant-ageing, reverse-ageing and life extending therapies. “Dehydroepiandrosterone is a steroid hormone precursor that is being sold under the table as an anti-ageing dietary supplement. Many medical entrepreneurs prescribe human growth hormone (HGH) for cell rejuvenation. HGH is a naturally occurring hormone produced by the pituitary gland. While it helps repair brain and organ tissues, it is illegal,” says Dr Praveen Bharadwaj, Consultant - Dermatology, Manipal Hospitals, Whitefield, Bengaluru.

Surgery for the youthful look has grown by leaps and bounds with platelet rich plasma combined with small amounts of neuromodulators and hyaluronic acid delivered to the skin using handheld needles. The result is the kind of improved complexion previously acquired using lasers—a process called the ‘vampire facial.’ “In 2016, I might have done botox treatment on 10 patients, which has gone up to around 40 in the last one year,” says Dr Hussain. The age of his botox patients is between 40 and 60 years. “The over-60 population come for treatments against wrinkles and pigmentation, and for jaw tightening, face lifting and laughter lines. There’s a 60 percent rise in this age group,” 
he adds.

Dr Singh, whose Yuva Biosciences is developing remedies, which can prevent, slow down or reverse skin ageing and hair loss, argues that even as anti-ageing is growing into a multi-billion dollar industry in the West, in India the cultural norms have made it into an ethical debate. “Ageing is now considered as a disease. So the industry is developing drugs just like they did for diabetes,” he maintains, stating that anti-ageing treatments in India should come under the purview of the age-old tradition of Kaya Kalpa.

Agrees Monimita Sarkar, Founder, Unmukt-The Senior Hub, a platform working in the senior care industry, “Almost all of our members are financially independent and if they want to spend money to look good or stay healthy then there shouldn’t be any ethical dilemma. We, Indians, need to come out of this mindset that once you are old, you don’t need to worry about looks. We are trained to think that our consumption should go down as we age. However, nobody is challenging death.”
The paradigm has shifted from extending life to extending youth. And it seems to be working.

Eighty is new hundred.
Dr Mukta Ahuja, Gurgaon-based biopsychologist, cautions: “With a large community of biohackers promising that they can double your lifespan through stem cell therapy, gene hacking, hyperbaric oxygen therapy, blue light blockers etc, the obsession with longevity is taking a dangerous turn as there are hardly any credible clinical trials happening nor is there concrete evidence about their efficacy. The side-effects, on the other hand, could take whatever is left of your life rather than add to it.”

Laboratories as Incubators of Youth: Genetic reengineering and advanced surgical procedures are leading the youth rush.  The challenge as we age is to retain a sharp mind and healthy body. Some scientists treat aging as an illness. Steven Austad, a distinguished biology professor at the University of Alabama, says the key to a longer life is to prevent our molecules from ageing. A compound that reverses ageing, a drug cocktail that shaves years off your biological life, mixing chemicals with baker’s yeast, nano robots that can be injected into the body to seek and destroy cancer cells by cutting off their blood supply are some of the hundreds of successful experiments in the quest for eternal youth. Said Austad in a TED talk, “Can you imagine what you would do if you could live your peak years—your 20s and 30s, say—over and over? Maybe we use the [extra] years to reimagine the trajectory of life, just like we did 100 years ago, when we invented childhood and retirement.”

Findings of a year-long experiment, published last month in Aging Cell, showed that participants shed 2.5 years of their biological ages by taking a carefully curated cocktail of a growth hormone and two diabetes medications. Their immune systems showed signs of rejuvenation. Their epigenetic clocks, based on the body’s epigenome—millions of chemical compounds and proteins that attach to DNA and basically direct the genes what to do—slowed down. Chemical experiment nets are ongoing to leverage alpha-ketoglutarate, which extends life and health span in mice and slows ageing in humans. A compound, name withheld, that escalates physical fitness levels, prevents obesity and increases healthy life span in mice is on track to get FDA approval in four years. Cancer studies and research on Alzheimer’s have thrown up possible anti-ageing solutions. Cell rejuvenation is a prime segment of anti-ageing research. As Adam Gabbatt wrote in The Guardian, “The aim, as many in the ‘physical immortality community’ put it, is to: ‘Live long enough to live forever’.”

Money for Life: The importance of unique age engineering therapies is revealed in the number of new companies receiving millions in funding. Billionaires Jeff Bezos and PayPal co-founder Peter Thiel have invested in San Francisco-based Unity Biotechnology, which aims to “extend human health span—the period in life unburdened by the disease of aging.” Obviously, Bezos, the second billionaire to travel to space, doesn’t want to grow old—previously he had invested in the San Francisco-based Unity Technologies that is working on developing anti-ageing therapies. Life extension startup Juvenescence, founded by British billionaire Jim Mellon, has invested in the California-based AgeX Therapeutics, which is using stem cell therapy to regenerate aged tissues.

Another UK company, Altos Labs, has got $270 million to work on biological reprogramming technology to prolong human life. Russia’s Insilico, whose mission to apply AI to extend productive longevity, has raised $306.3 million. Neuraly, a Johns Hopkins School of Medicine spinoff whose aim is to invent the first, disease-modifying agent for neurodegenerative disorders and aging, has received $36 million. US biotech firm Elevian, which develops drugs that restore the body’s regenerative capacity for youth to treat and prevent age-related disease, has raised $29 million. There are a host of companies in the life extension business, all with different approaches. Elisium Wellness will produce the world’s first cellular health supplement. Edifice Health uses AI to change the course of the ageing process. Bioquark Inc will regenerate and repair damaged human organs and tissues by remodelling them. Singapore-based Gero reverse-engineers cells to extend a healthy lifespan and delay chronic age-related diseases.  “We are here to solve aging,” is their motto. Ironically people with greater wealth, even siblings, live longer than their poorer counterparts.
 
Beauty Goes Skin Deep: Aesthetic medicine is no longer just about botox injections and fillers. Lasers, micro-needles and unique fillers are minimally invasive treatments that rule the cosmetic medical space. Specialists are injecting PRP taken from the patient’s own body into the scalp to fix damaged hair follicles for a thicker fuller head. New soft tissue fillers popular in Europe are leading the fillers market. The versatile picosecond lasers have both wide and specific use—they aid overall skin rejuvenation and brightening as well as removing or reducing fine lines, brown spots, melasma, acne scars, and unwanted tattoos. Ultherapy uses microfocused ultrasound to stimulate collagen, thereby tightening the skin to prevent it from sagging.

The millennials have wised up to the fact that prevention is better than surgery and hence are choosing treatments that will delay the aged look by some years. Catch them early is the millennial beauty ethos. Early use of neuromodulators like botox and fillers in smaller quantities has been clinically proved to slow aging, but mildly and gradually. It also cuts down on future maintenance. The pout is still sexy—aesthetic surgeons are asked to create “couture lips” for clients more than other procedures. Combining radiofrequency with microneedling is a blood-free process with fast recovery. Adding red and blue LED light to RF microneedling is an acne killer and enhances skin brightening.

Dr Singh of Yuva Biosciences has demonstrated that protecting and boosting the function of the mitochondria, the powerhouse of cells, make wrinkles disappear and restore hair growth. His study was published in the Nature journal a few years back.

“A woman’s ovaries age much earlier than her actual age. So we are currently focusing on ovarian ageing with an eye on delaying menopause in women and extending reproductive longevity. Since mitochondria dysfunction is one of the hallmarks of ageing, our laboratory is utilising the mouse model on disrupting mitochondrial function in a tissue and investigating it for ageing,” Dr Singh says.

The End of Liposuction? Botox is even used to relieve pain in people, whose jaws ache when chewing food, and who grind or clench their teeth, in one to two weeks. Body contouring has expanded to include non-surgical techniques. New technology has enabled people to opt for non-surgical body sculpting options to get six packs, well-defined buttocks, skin tightening and lymphatic drainage massages. A process pioneered by South Korean dermatologists, botulinum toxin injections are subcutaneously delivered to achieve slim necks and completely remove fat from thighs. The effects, visible in four to six weeks, can last up to six months. The effect of bespoke polylactic acid injections last two to five years, and fixes cellulite, stretch marks, and loose skin. Cosmetic surgeons are going beyond results that can be achieved in a gym by refining muscles using procedures that exercise key core muscle groups. No more liposuction even for people with BMIs under 25.

Perils of Immortality: However, living forever may not prolong the life of the planet. Further overpopulation will strain an already strained healthcare, necessitate creation of more jobs, food and housing that will lead to the over-exploitation of resources that has ignited climate change. It will cause deep divisions in society between the wealthy and the poor, eventually leading to a dystopian society. Ahuja says, “This obsession with ‘forever’ is nothing but humanity’s failure to come to terms with dying. Even though eternal youth has been our preoccupation for millennia, we hardly talk about or understand death. Because we don’t want to face death, we have to find a way around it by prolonging life.”

The benefits of ageing are ignored in the search for back to the future. Writes American author Ephrat Livni, “For a personal sense of wellness, we may still be better off thinking of ageing as an inevitable process with certain positive aspects—like additional wisdom accumulated through experience—rather than a sickness we hope to eradicate. If the many startups working on extended youth and anti-ageing endeavours actually manage to create a magic potion that keeps us forever young, then someday we may get the chance to think about what, if anything, humanity loses when it finally finds the fountain of youth.”

Immortality is the hazy twilight where myth and history overlap with bizarre consequences. The first emperor of China sent out explorers to look for the elixir of life. French aristocrats in the 16th century put gold in their drinks to prolong their life. Cleopatra bathed in asses’s milk. The Hungarian countess Elizabeth Bathory murdered young women and bathed in their blood to live forever. A girl on MTV bathed in pig blood to stay young.

In the Sumerian poem, ‘The Epic of Gilgamesh’, considered the earliest surviving notable literature and the second oldest religious text, the eponymous Sumerian king who sought and found the magic herb of immortality is cheated by a serpent, which eats it. Challenging Nature is as old as prehistoric humans who hunted large animals with wooden spears. With the traps she lays for men, winning is another matter altogether.

Age extension therapies

Reprogramming Cells Ageing cells that stop copying themselves lead to growing old and eventually death. A research team led by prominent geneticist Dr David Sinclair successfully reprogrammed mice cells, thereby reviving old cells. This process is called REVIVER (recovery of information via epigenetic reprogramming), which proved that old cells store information that can be used to reverse age.

Regenerate and Revive Tissue and organ regeneration company LyGenesis has regrown functioning organs in a patient’s lymph nodes using cellular therapy. This means that tissue can be regrown from one organ, for example a liver, to grow multiple livers for patients waiting in line for a transplant. Organ regeneration is calculated to prolong life till to 200 years.

Mind Over Machine Rewire Neuralink, owned by Elon Musk, is working on mind control of computers and other machines. Beneficiaries will be Parkinson’s patients—human trials on paraplegics using their thoughts to make machines perform tasks will commence soon. 

Taking Time Back Legendary scientist Steve Horvath visualised the epigenetic clock, which analyses the predictable changes in our genes to calculate our biological age. By using the clock and experimenting on the human organ  system that includes the nervous system, cardiovascular system, digestive system, skeletal system and more, researchers reversed the biological age of participants in an experiment by an average two-and-a-half years in a year. Their immune system showed signs of renewal.

Editing the System A uniform cure for all diseases? A new generation of genome editing called Prime Editing could allow scientists to edit and correct many genetic mutations (89 percent) in its purview.  

Bioscientists have arrived at the maximum human lifespan but billions are being spent on life extension projects. Experts estimate that the person who will live beyond 150 years has already been born.
 



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