Molecular mechanism behind aging unveiled

From an evolutionary standpoint, aging makes no sense. Why deteriorate over time, when you could simply reproduce forever? How does it benefit us to grow older?

A 2017 paper co-authored by Jonathan Byrne and Thomas Wilhelm from Germany’s Institute of Molecular Biology (IMB) published in the research journal Genes & Development presents some of the first concrete evidence for the evolutionary roots of aging.

Scientists have long questioned the biological function of aging.

One of the first probable explanations was put forth in 1953 by an evolutionary biologist named George Williams, who proposed the hypothesis of antagonistic pleiotropy (AP).

Pleiotropy is when one gene controls more than one phenotypic, or observable, trait. Antagonistic pleiotropy is when one trait has a positive effect on the organism while the other trait has a negative effect.

AP is involved in numerous genetic disorders, from Laron Syndrome, which causes dwarfism, to Huntington’s disease, a neurodegenerative disorder. The context in which Williams originally proposed AP had to do with aging.

Williams theorized that natural selection favors genes which improve reproduction, ignoring the detrimental impacts of those genes so long as they occur after reproduction begins.

In other words, a longer life is the opportunity cost of having a greater number of healthy offspring, and it is an cost evolution is willing to pay.

Byrne and Wilhelm, who conducted their research on Caenorhabditis elegans roundworms, recently provided evidence to support Williams’ hypothesis.

“The evolutionary theory of ageing just explains everything so nicely but it lacked real evidence that it was happening,” Byrne said, according to ScienceDaily.

One difficulty scientists in this line of research have faced is the challenge of working with old animals.

“From a relatively small screen, we found a surprisingly large number of genes that seem to operate in an antagonistic fashion,” Byrne said, according to ScienceDaily.

The 30 genes the researchers discovered were also some of the first to be identified that were responsible for aging in worms that were older.

So what exactly do these genes do?

“We found a series of genes involved in regulating autophagy, which accelerate the ageing process,” Principal Investigator Holger Richly said, according to ScienceDaily.

Autophagy is the process by which cells degrade and recycle their own components, the cellular version of cleaning house. It is a function that is known to decrease as an organism grows older.

“It’s classic AP,” Richly said, according to ScienceDaily. “In young worms, autophagy is working properly and is essential to reach maturity but after reproduction, it starts to malfunction causing the worms to age.”

Richly and his team made a second discovery as well. It was commonly believed that even barely functioning autophagic processes are superior to non-functioning ones, but the researchers demonstrated that turning off genes that regulated autophagy actually extended the worms’ lives.

“There are severe negative consequences when it [autophagy] breaks down and then you are better off bypassing it all together,” Richly said, according to ScienceDaily.

Deactivating autophagy specifically in the neurons proved to be the most beneficial. It resulted in worms that not only lived longer but remained healthier.

“Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age who you then live longer than,” Wilhelm said in an interview with ScienceDaily. “We turn autophagy off only in one tissue and the whole animal gets a boost.”

Beyond aging, the research is projected to impact other diseases associated with malfunctioning autophagy in the neurons — diseases as prominent in the public’s imagination as Alzheimer’s and Parkinson’s.

“It is possible that these autophagy genes could represent a good way to help preserve neuronal integrity in these cases,” Wilhelm said.