What's Behind the Aging Process?

By Jane Farrell

Researchers at the Institute of Molecular Biology (IMB) in Mainz, Germany, have made a breakthrough in understanding the origin of the aging process. They have identified that genes belonging to a process called autophagy – one of the cells most critical survival processes – promote health and fitness in young worms but drive the process of aging later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the aging process arises as a quirk of evolution.

These findings may also have broader implications for the treatment of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease where autophagy is implicated. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole-body health.

Getting old: It’s something that happens to everyone and nearly every species on this planet, but the question is, should it? The laboratory of Dr Holger Richly at IMB, has found some of the first genetic evidence that may put this question to rest.

As Charles Darwin explained, natural selection results in the fittest individuals for a given environment surviving to breed and pass on their genes to the next generation. The more fruitful a trait is at promoting reproductive success, the stronger the selection for that trait will be. In theory, this should give rise to individuals with traits which prevent ageing as their genes could be passed on nearly continuously. Thus, despite the obvious facts to the contrary, from the point of evolution aging should never have happened.

This evolutionary contradiction has been debated and theorized on since the 1800s. It was only in 1953 with his hypothesis of antagonistic pleiotropy (AP) that George C. Williams gave us a rational explanation for how aging can arise in a population through evolution. Williams proposed that natural selection enriches genes promoting reproductive success but consequently ignores their negative effects on longevity. Importantly, this is only true when those negative effects occur after the onset of reproduction. Essentially, if a gene mutation results in more offspring but shortens life that’s fine. This is because there can be more descendants carrying on the parent’s genes in a shorter time to compensate. Accordingly, over time, these pro-fitness, pro-ageing mutations are actively selected for and the aging process becomes hard-wired into our DNA. While this theory has been proven mathematically and its implications demonstrated in the real world, actual evidence for genes behaving in such as fashion has been lacking.

This evidence has now arrived, according to Jonathan Byrne, the co-lead author of the paper, “The evolutionary theory of aging just explains everything so nicely but it lacked real evidence that it was happening in nature. Evolution becomes blind to the effects of mutations that promote aging as long as those effects only kick in after reproduction has started. Really, aging is an evolutionary oversight.”