Will age be just a number?

American polymath Benjamin Franklin once wrote: “...in this world, nothing is certain except death and taxes.” Well, taxes may remain a certainty in life but death, in the future, can become an opt-in feature.

Turning the clock back, a team led by molecular biologist David Sinclair of Harvard Medical School, according to a recent media report, has managed reverse ageing in mice by employing proteins that can turn an adult cell into a stem cell. The lab rats are real-life Benjamin Button!

In an earlier breakthrough, published in late 2020, the team restored the damaged retinas of old mice and improved their vision to new-born levels.

“It’s a permanent reset, as far as we can tell, and we think it may be a universal process that could be applied across the body to reset our age,” Professor Sinclair was quoted as saying in the CNN report. “If we reverse ageing, these diseases should not happen. We have the technology today to be able to go into your hundreds without worrying about getting cancer in your 70s, heart disease in your 80s and Alzheimer’s in your 90s.”

Professor Sinclair said his team has reversed ageing in mice muscles and brains since the initial study, and now they’re working on regenerating the entire body of a mouse.

How to reverse the ageing process and extend life expectancy is a scientific question that has attracted enormous attention and huge investment in recent years. But before exploring reverse ageing, it is necessary to understand how our cells age.

The second law of thermodynamics says, in simple terms, entropy (or gradual decline into disorder) always increases. This principle explains, for example, why one cannot un-burn a matchstick or why death is inevitable. The longer we live, the more our bodies decline into disorder: Mutated genes and uncontrolled transposable elements — sequences of DNA that move (or jump) from one location in the genome to another, potentially scrambling our genes.

As entropy runs its course, the only question remains which part of our body will give up first or which age-related disease shall strike first. According to biogerontologist Leonard Hayflick: “Good health is merely the slowest possible rate at which one can die from an age-associated disease (Handbook of Theories on Aging).”

According to the World Health Organization, the global average life expectancy of a human is 73.4 years (as of 2019). Scientists are of the view that if all age-related diseases vanish, the average human life expectancy shall jump to 89 years; still, there will be no escape from death. This is because our cells have an expiry date, written in our chromosomes.

Telomeres — the protective DNA caps at the end of chromosomes — keep an eye on the damage that accumulates in our cells and signal when it is time for them to retire. A little bit of telomere is lost each time a cell divides, and telomerase, the enzyme that maintains caps, isn’t typically active in adult tissues.

According to a report in Science, it has been seen that people with longer telomeres live longer, healthier lives, whereas those with shorter telomeres suffer more from age-related diseases, such as diabetes and heart disease.
 

According to Professor Hayflick, cells enter senescence after dividing 40-60 times. It is mainly due to shortened telomeres. But this problem can be solved: In lobsters, cells can go on dividing forever because, in them, the enzyme telomerase constantly rebuilds telomeres. So, why not we, humans, take shots of telomerase? There is the threat of cancer (cancer cells produce a lot of telomerase; they never die but kill the person having them, instead).

So why not rein in our transposable elements or jumping genes? The freshwater hydra keeps them in check and maybe with more research, this simple animal can teach us a lesson in life extension.

There is another way popular among scientists —reprogramming of cells.

Professor Sinclair’s team’s aforementioned breakthrough is not the first in the so-called “anti-ageing” research. Nobel Prize-winner Shinya Yamanaka laid stepping stones in 2006 when he discovered how intact mature cells in mice could be reprogrammed — by introducing a group of four protein transcription factors known as Yamanaka factors — to become immature stem cells that are able to develop into all types of cells in the body. The problem with this technique is: Adult cells lose their identity when they are switched back to stem cells.

In another key study (published in Cell in 2016), researchers at Salk Institute for Biological Studies reversed the signs of ageing in mice without erasing the identity of cells. But later it turned out that the mice used in the research developed cancerous tumours under certain conditions.

Given the current limitations, we appear to be far from conquering ageing. In the meantime, we must prepare for the consequences. The world has to be ready to feed, take care of, and provide job opportunities to millions or billions of humans with extremely long life-lines. 

Also, we'll have to find the answer to another important question: What will we do when we become immortal and age is just a number?