IS GROWING OLD GETTING OLD?

Maribel Schonewolff on why we age and how we might combat senescence in the future.

When I asked my friends to brainstorm about ageing their first responses were “white hair, wrinkles, no teeth”, “calm and wise grandparents”, “no sex”. These associations are quite common and show that aging is mostly referred to as something negative – at least by younger generations: a decline in activity, health and fun. With society growing older and older in many countries, both the anti-aging industry and biomedical sciences are continuously challenged to come up with ways to stall one of the greatest mysteries and most natural frontiers of life: the aging process.

The mystery of aging has two components. How is my life going to change as I get older? And, when will I die? We can attempt to answer the latter using a nation’s average life expectancy. For example, a child, born in the UK in 2020 will live for 81 years on average. The oldest woman to ever have lived was probably the French Jeanne Louise Calment, who allegedly died in 1997 at the age of 122, which is close to the suggested maximum human lifespan. So, what is the highly sought-after secret to a long life?

It’s commonly accepted that both lifestyle and genes heavily influence our lifespan. The existence of so-called blue zones in Italy, Japan or Costa Rica with extraordinarily high numbers of centenarians (people who are a hundred years old or more) who share dietary habits or rare genetic mutations supports this hypothesis. It does not come as a surprise that Disney Star Zac Efron left Hollywood to explore these magical places and unravel the secret of a long and healthy life far away from Botox and protein shakes in his Netflix travel and lifestyle documentary.

But let’s check the facts: what do we really know about aging on a scientific level?

For a molecular biologist, aging is the decline of organismal integrity and cellular function over time. “But that’s another quite negative and complicated definition that makes me want to join Zac in eating pasta and drinking litres of goat milk” you might think. The central question of aging science is to understand how and why we age. Because it is a relatively new discipline, aging research follows an efficient bottom-up approach, aiming to understand basic biological principles in healthy organisms and use this knowledge to explain dysfunction in age-related diseases. It is commonly accepted that important maintenance mechanisms in our bodies break over the course of a lifetime. The loss of cellular repair mechanisms leads to an accumulation of more and more damage until the body has reached its limit and dies.

The nine most prominent age-related defects were grouped in a paradigm-defining 2013 article by Lopez-Otin titled “The Hallmarks of Aging”. They include mechanisms responsible for growth control and nutrient perception, regulation of energy metabolism, immune system and microbiome influence, DNA replication and protein homeostasis. Aging researchers use model organisms like fruit flies to investigate the impact of random or targeted manipulations of their genome sequence. Through such manipulations, small point mutations help identifying genes that play a role in maintaining crucial functions, like preventing uncontrolled growth of oncogenic (pre-cancer) cells. Such findings from basic organisms can be translated to more complicated animals like humans, if genetic programs and molecules are conserved throughout evolution.

Current efforts vary from administering vitamin supplements to the round worm C. elegans, a model for improving protein quality control mechanisms, to studying the naked mole rat, which never gets cancer. Researchers from the Max-Planck-Institute for Biology of Aging in Germany showed the life expectancy of fish increased when their old microbiome was removed with antibiotics and their gut was recolonized with bacteria extracted from the excrements of younger fish.

Now it is up to you if you will “store a bag of your young poop and keep it for later” as the lead scientist in this study, Dario Valenzano, jokes about in a TV interview. It remains to be understood what exactly the essence of a long and healthy life might be, but it is clearly fascinating to explore the frontiers of life(span) where nature performs its miracles with molecular precision.

Maribel Schonewolff is studying for a PhD in Biochemistry at Wolfson College.

Artwork by Ralf Zeigermann.