The biology of ageing

Why are we programmed to grow old and die? 

Writer: Bethany Evans
Editor: Elly Chaw
Art: Ki Wangyu

“Eternal Youth” is an idea that has captured our imaginations for centuries, and is evidently deeply embedded in legends and mythologies. In Norse mythology, the character Iðunn provides Gods with apples that grant them eternal youth. In the story of Tithonus, a character asks the Gods for immortality, but makes the foolish mistake of forgetting to ask for eternal youth too. While our life spans have certainly increased since the time these mythologies were composed, we still grow old. And we still die. But why?

Contrary to the idea that we humans were “designed” in a way that makes death inevitable, and that it is “programmed” in our genetics to grow old and die, it is actually widely accepted by scientists today that ageing is not a genetically-programmed process; it is not like the developmental processes that cause growth and maturation of organisms. Instead, ageing is the result of failure – failure of the molecular mechanisms that maintain cell and organ homeostasis, until eventually, we grow “old” and we die.

So, what are the mechanics of ageing? That, I’m afraid, scientists have not yet reached a consensus on. However, there are several leading theories.  

One such theory argues that following the reach of sexual maturity, we gradually accumulate mutations that result in our own progressive decline. In other words, we gradually accumulate mutations that result in ourselves “ageing”. Antagonistic Pleiotropy Theory, conceived by George Williams in 1957, takes this concept even further. According to Williams,  mutations favoured early on in life that promote positive effects (like reproductive success) and are selected for have harmful effects later in life. In other words, some genes  “enhance” our fitness when we are young, but then reduce it as we get older. Ageing, then, becomes the inevitable side effect of a successful youth. In 1984, scientist Michael Rose confirmed this theory as observed in the vinegar fly, Drosophila melanogaster. He demonstrated a close link between early fertility and lifespan, where a selection for genes that translated to early fertility resulted in shorter lifespans, and a selection for genes that translated to late fertility resulted in longer lifespans.

Alternative theories argue that ageing is more of a failure in mechanisms, rather than an evolutionary failure. Oxidative Damage Theory is one such theory. This theory was the first of its kind to suggest that the molecular mechanism of ageing involves the oxidative damage of vital biological macromolecules (such as DNA) by reactive oxygen species. Mitochondrial Free Radical Theory furthered this notion, identifying the reactive oxygen species produced via metabolic processes in the mitochondria as the main species that causes this oxidising damage. The more “damaged” our biological molecules get, the more we progressively decline in terms of fitness, until we eventually die.

Telomeres (repetitive DNA sequences at the end of chromosomes) are of scientific interest too, in the pursuit of underpinning the mechanisms of ageing. Telomeres at the end of your chromosomes protect your DNA from accumulating damage. However, each time a cell divides, pieces of DNA are lost at the end of the chromosomes, in a condition known as “telomere attrition”. Hence, chromosomes are no longer protected by these telomeres, generating genomic instability. DNA can now accumulate damage, leading to cellular ageing and eventual cell death.

But all hope is not yet lost! Telomerase is an enzyme that synthesises telomeric sequences at chromosome ends, using RNA as a template. Extending telomere length in this way has been shown to expand lifespan. Studies in gene-targeted mice have shown that reactivation of telomerase decelerates ageing and improves health span. Maybe this is the beginning of bottled “Eternal Youth”?

Whatever theory prevails, it is clear that this is a “hot topic” in science, with our understanding of the mechanisms of ageing growing every passing day. Perhaps even one day, we might be able to grasp this “Eternal Youth”  as described by those ancient mythologies. If biologically immortal creatures such as starfish can do it, why can’t we?

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