End of Ageing

Eternal life is still fantasy, but advances in medical science could turn back the clock on your physical age sooner than you think.

All through history, across cultures, humans have shared a thirst for eternal life. In the Epic of Gilgamesh, saddened by the death of his friend Enkidu, the Mesopotamian hero-king sets out on a quest for the secret of immortality, a rejuvenating flower that brings back youth. In the Mahabharat, cursed by the sage Shukracharya, the king Yayati ages prematurely until his son Puru renounces his youth for him. In Ancient Greece, Elysium, the island of the blessed, was home to the immortals. And Adam and Eve, of course, were immortal before the Fall.  

Only the Buddha, ever the pragmatist, had cautioned, “With the arising of birth, there is the arising of ageing and death.” Ageing, he said, is as inevitable as death, or perhaps even more so. For, to be born is to be subject to ageing. But what if it were not so? What if the ancient quest was realisable? 

Advances in modern science are indeed close to making this possible. If not an end to death, we are within sight of an end to ageing. Not only may we be able to stop and even reverse some of the effects of ageing, we may well be able to ensure that in doing so, we preserve a quality of life we had in our youth.  

In 1917, Osborne, Mendel and Ferry found that rats fed on a calorie-restricted diet actually gained in lifespan. Since then, the experiment has been repeated on fruit flies, spiders, guppies, rats and rhesus monkeys, with much the same result. The consistency of results across species has led to the expectation that calorie restriction may have the same impact on humans. 

In a recent paper in The Federation of American Societies for Experimental Biology (FASEB) journal, Trygve Tollefsbol’s team at the Center for Aging at Birmingham, US, has reported how restricted calorie diets actually help human cells live longer. The researchers used both normal human cells and precancerous cells on the verge of cancer formation. Both sets of cells were grown in the laboratory and received either normal or reduced levels of glucose. As the cells grew over a period of a few weeks, they found that when given less glucose, the normal cells lived longer and many of the precancerous cells died. 

The problem is that the discipline required for living in a state of near starvation is not given to most humans, and most of us are bound to feel that a life extended at such cost is not worth living at all. But what if a drug could mimic the manner in which calorie restriction works? It may be less than a decade away. Says Tollefsbol, “We would… hope for these studies to lead to improved prevention of cancer as well as many other age-related diseases through controlling calorie intake of specific cell types.”

This information feeds into work being done by others, such as Professor Stephen Spindler at the University of California, who are screening drugs to check those that mimic the effect of a calorie-restricted diet. “The technique we have developed allows us to screen a relatively large number of drugs in months rather than years,” says Spender, “The hope is that these drugs will be able to extend the lifespan of healthy animals, and possibly, after further testing, healthy humans.” 

His team has already found a diabetic drug that seems to produce some of the beneficial effects of a low-calorie diet. It is a safe bet that the first such drugs will hit the market within a decade. Gerald Weissmann, editor-in-chief of FASEB, is categorical: ‘Western science is on the cusp of developing a pharmaceutical fountain of youth. This study confirms that we are on the path to persuading human cells to let us live longer, and perhaps cancer-free, lives.’

Brooke Greenberg is a 16-year-old living in the body of an 11-month-old infant. She can make gestures and noises to express her desires and her brain barely allows her to recognise her mother. Her bones, going by the level of the development of bone cells, are around 10 years old, and she still has all her baby teeth. 

Brooke’s is not an enviable fate, but it may well hold the key to ageing. Or so believe Richard Walker and his team at the University of South Florida. In a paper in the journal, Mechanisms of Ageing and Development, they have ruled out any known conditions that could explain Brooke’s state. They believe the best explanation for her condition lies in an unidentified gene, or group of genes, that regulate ageing in the body. 

According to Walker and his team, ‘Due to the extreme rarity of her disorder, characterization of the mutation and causative gene(s) is likely to be elusive. However, with completion of the Human Genome Project and sequencing of the entire genome… it may be possible using subject’s DNA to better understand the developmental process and possibly to also extend youthful lifespan by silencing expression of the “senescence regulator gene”.’ 

Just for a moment, consider what would become possible if the age regulator is identified. Who would say no to living as an 80-year-old with the brain of a 30-year-old and the bones and teeth of a 20-year-old? 

Detecting a gene or several genes that regulate ageing may only be a fraction of all that is made possible by mapping the human genome, an achievement that will eventually count on par with germ theory or the discovery of antibiotics in the history of medicine.

Consider a hypothetical disease controlled by a cluster of ten genes: say, a person with all ten genes of a certain type will definitely have the disease, while someone with none of these genes will not have the disease whatever his or her lifestyle. Most people will lie somewhere in between, and for them lifestyle choices could be crucial in triggering the onset of the disease. Gene sequencing will eventually offer them knowledge of what awaits them long before the disease becomes manifest. 

This model applies to a host of ailments such as diabetes, heart trouble, hypertension and cancer, which is why medicines will soon differ even for individuals who share the same symptoms. The same drug that could help one person may not benefit another. 

Complete personal genetic profiling will be key to the administering of medicine in the future. Treatment will not simply be a question of what medicine works best against a particular disease, it will be a question of what medicine works best for your affliction given your specific genetic profile. 

The US company Champions Biotechnology already provides an extreme example of how such custom treatment would work. Tumours from cancer patients are implanted in immune-deficient mice; these produce rat tumours that preserve the biological characteristics of the original human tumour. Oncologists then study the response of this tumour to a specific combination of chemotherapy drugs, allowing the combination that works best to be used for the particular patient. 

According to an article in The Scientist, ‘… Champions has successfully implanted tumors from 15 patients in mice, and completed drug studies on seven. Six of the seven, having already failed standard chemotherapy regimens, nonetheless responded—for time periods ranging from 9 months to over 3 years (three are still living)—to drug combinations their tumorgrafts predicted would be effective. (The company has not compared this data to matched controls, but the historical response rate to any drugs in patients who have failed conventional therapies is 5 per cent or less.)’

At the moment, this treatment does not come cheap. The company charges $100,000 (Rs 47 lakh) for creating a tumour graft. But in future, the idea of personalised medicine would be to anticipate and ward off cancer before it strikes. This would require two things: rapid and relatively cheap genomic analysis as well as a digital database of potential genetic problems. The simple check-up we undergo today—blood pressure and a few blood tests—would give way to far more detailed genetic analysis, which in all likelihood would be based on a pinprick of blood.  

However thorough the methods of prevention, there will be no shortage of ailments and medical conditions that require a cure. People will continue to be born with type I diabetes and other congenital diseases, and despite the best care in the world, human organs will age and heart attacks will occur.  

So far, the methods used to treat such problems have fallen short of a complete cure. Type I diabetes requires a lifetime of insulin injections, and organ transplants are constantly beset by fears of rejection by the host body even if donors can be found.

But a whole class of medical techniques promises to change this. Subsumed under the title of ‘regenerative medicine’ are methods that hold out the promise of repairing damaged tissue and organs within the body, as well as growing them in the lab. Enter the bioprinter, which actually promises to replicate human organs. Human cells are first placed on very thin sheets of gel to form a layer of the organ, and these layers are then ‘assembled’ to create the required organ based on a pre-existing mould. 

This is not science fiction. A California-based company Organovo has already brought out a prototype that can grow new arteries. 

“Scientists and engineers can use the 3-D bioprinters to enable placing cells of almost any type into a desired pattern in 3-D,” says Keith Murphy, chief executive of Organovo, “Researchers can place liver cells on a preformed scaffold, support kidney cells with a co-printed scaffold, or form adjacent layers of epithelial and stromal soft tissue that grow into a mature tooth. Ultimately, the idea would be for surgeons to have tissue on demand for various uses.” 

A recent US Department of Health and Human Services report has put down some feasible benchmarks. The report says: ‘Regenerative medicine could begin producing results within 5 years. At the 5-year mark, complex skin, cartilage, bone, and blood vessel products would begin to reach markets. Within 10 years, organ patches that repair damaged tissues would potentially be available. Within 20 years, full organ regeneration is a strong possibility.’

Quite apart from every other advance in healing, there is one organ that is crucial to our health but whose astounding abilities to heal are still poorly understood—the brain. 

Consider what science calls the placebo effect, where the body responds to what is basically a sugar pill, by harnessing its own defence mechanisms. Its effect seems to be growing stronger with time. A recent study has reported that the number of new drugs rejected after being tested against placebos has risen 20 per cent. Not only that, repeat clinical trials of drugs such as Prozac are showing that the placebo effect is actually growing stronger in a measurable way: the placebo showed more success in recent tests. No one is sure of why this is so, but one reason could be increasing faith in the power of modern medicine. 

It is believed the placebo effect comes about because the brain responds to thoughts and moods by producing neuro-chemicals, which in turn affect the body’s ability to fight disease. The process is poorly understood, but even at this early stage, this ability of the mind is being harnessed in innovative ways.

According to a study published in the journal Psychosomatic Medicine, researchers have been able to treat psoriasis patients with a quarter to one-half of their usual dose of steroid medication by mixing placebos with the steroid. Psoriasis is a chronic condition involving the immune system which is exacerbated by stress. Various factors can cause the immune system to trigger overproduction of skin cells, resulting in red, scaly patches of dead skin. A similar approach should work for other chronic diseases that involve the mind or the immune system, such as asthma and multiple sclerosis.

“Our study provides evidence that the placebo effect can make possible the treatment of psoriasis with an amount of drug that should be too small to work,” says Robert Ader, professor at the University of Rochester School. “While these results are preliminary, we believe the medical establishment needs to recognise the mind’s reaction to medication as a powerful part of many drug effects, and start taking advantage of it.”

Of course, all the advances against ageing will have little meaning if the mind does not remain healthy. Already, as more and more people live to an older age, one of the greatest health challenges has been the cognitive impairments that impact the quality of life of the aged. Many of the aforesaid techniques work in similar fashion for the brain. 

Stem cell therapy has already shown some promise in repairing damage, and dormant brain stem cells could be awakened to produce neurons. Gene sequencing should soon be providing information on a host of disorders. 

Speaking to The Times of London about his prediction for the future, James Watson, who discovered the structure of DNA along with Francis Crick, said, “Disorders like Alzheimer’s disease, epilepsy, Parkinson’s disease, schizophrenia, bipolar disease, unipolar depression, obsessive-compulsive disease, attention deficit disorder and autism will finally have their genetic guts open for all to see.”

But perhaps the most ambitious prediction was made by Henry Markram, director of the Blue Brain Project at the Ecole Polytechnique Federale de Lausanne in Switzerland. In April this year, he announced that his team has been able to recreate the functioning of a real brain through a detailed molecule-by-molecule simulation of a slice of the brain. The simulation, he said, “starts to learn things and starts to remember things. We can actually see when it retrieves a memory, and when they are retrieved from it”.

By 2020, he told The Times, this simulation should be good enough to ensure “we won’t need a psychologist to tell us why we feel unhappy. All we’ll need to do is log into a simulation of our own brain, navigate around in this virtual copy and find out the origins of our quirks… Computers will look at a virtual copy of our brains and work out exactly what we need to stop our headaches, quiet the voices talking in our heads and climb out of the valley of depression to a world of colour and beauty”. 

An 80-year-old with the mind and body of a 20-year-old, who would say no to youth and experience?

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