Could the "powerhouse of the cell" be a fountain of youth?

By: Lee-Marie Raytek, Queen's University

Seeing as we’re all facing the ticking of our biological clocks, it’s no surprise that the global longevity economy was worth 17 trillion USD in 2019 and is expected to reach 27 trillion USD in 2026. Thanks to the last couple centuries of research, medicine, and improved hygiene, the average human life expectancy (at least in wealthier countries) has been on the rise. Naturally, the aging of our global population has stimulated research into the biology behind it and why it happens.

The buzz surrounding the free radical theory of aging has been at the center of many controversial debates in the last decade. Free radicals are molecules naturally produced in our cells that can damage us from the inside out. This is why scientists believe it contributes to aging - the more damage they cause, the shorter your lifespan. One variation of this theory was coined the “mitochondrial oxidative stress theory,” and seems to be a favourite of many. It suggests that it’s specifically the damage caused by free radicals to the mitochondria which speeds up the aging process. Despite this there is puzzling evidence that increased levels of free radicals may be connected to longer lifespan in some animals.

We still lack a clear answer as to how free radicals cause – or don’t cause – aging at the cellular level, but a recent study offers an intriguing perspective on the mitochondrial oxidative stress theory. By looking at free radical production and elimination in both naked mole rat and mouse mitochondria, researchers seem to have found some evidence to reconcile the two camps.

The naked mole rat is a fascinating study because of its hefty lifespan of around 30 years – remarkably long for a rodent. Most rodents like lab mice only live up to 4 years. Naked mole rats also seem to have high resistance against cancers and other age-related diseases compared to other rodents. When comparing the formation of free radicals in naked mole rats and mice, there is no clear-cut way of looking at the data. The issue arises when researchers try to “normalize the data.” This has to be done because it’s hard to directly compare the number of free radicals between the two animals.

Imagine paying $5 for Fuji apples or $7 for Granny Smith apples. But how many apples does that buy you? Or how many pounds of apples do you get? We want to know the price per pound of apples or the price per number of apples to accurately compare which is the more expensive of the two. To the scientist, the apples are the free radicals. That makes the “price” the amount of free radicals. So scientists want to know the “price” or amount of free radicals made per number of mitochondria in their sample so that they can compare which species generates more free radicals in their mitochondria.

Even after normalizing the data three different ways, the group has not found a consistent answer on free radical production: sometimes the data reveals that naked mole rats produce more free radicals, other times it looks as though mice produce more.

Excitingly though, there is a stark, unquestionable difference in free radical elimination – no matter how we look at the data. Naked mole rat mitochondria always show a higher capacity for getting rid of free radicals than mouse mitochondria do.

Instead of shutting down the process of generating free radicals in mitochondria, naked mole rats possess effective pathways to eliminate them. This finding sheds some light on why free radical production is not always directly correlated with lifespan depending on the animal. Instead, the extent of damage caused to the mitochondria must also depend on how quickly free radicals are eliminated.

The mitochondrial theory of aging remains intact – for now. Slowing the amount of damage caused by free radicals in mitochondria likely delays aging and increases healthspan in other animals, including humans. This new insight could potentially lead to the development of new therapies against age-related diseases, like a drug to enhance the ability of your mitochondria to eliminate free radicals. Our very own fountain of youth may turn out to already exist within mitochondria. We just have to figure out how to get its water flowing.

Edited by participants of the 2021 Science Writing Internship program and B.G. Borowiec. Header photo from Unsplash.