Reaching for immortality

“If you live to be one hundred, you've got it made. Very few people die past that age.”

~George Burns

When I was a graduate student, a new book appeared in the Zoology library called “The Genetics of Aging.” Although I hadn't aged that much, I was a student in the genetics program, so I figured I’d better read it. At the time (around 1980), there really wasn’t that much that could be said about mechanism, but the book made a strong case that there were key genes and pathways to be discovered and hinted at where to look for them.

One of the curiosities of aging for me is how large psitticine birds (parrots, macaws) are so long-lived (50-75 years) while similar-sized mammals only live a decade or less. I get why tortoises (cold-blooded, slow-moving) could live 100 years or more, or whale sharks (cold blooded, live in pelagic oceans at near freezing temperatures) could live for hundreds, but bird heart rates and metabolisms are far faster than mammals. There’s an interesting genetic puzzle to be solved.

Of course, breeding parrots is slow and expensive compared to breeding mice, fruit flies and nematodes. Plus, the genetics of these model organisms is sophisticated and the tools for genome modification are well-developed. Also, too, they share orthologs of the same genes and pathways that shape human development and metabolism. So the recent finding that modifying the expression of only two genes—both with human orthologs—can increase lifespan in the roundworm by five-fold (roughly the equivalent of a 400 year old person) is eye-catching.

In every animal it has been tested in, caloric restriction is the most consistent treatment to extend lifespan. Now, by “caloric restriction,” we’re talking about reducing caloric intake to about 60% of ad libitum, which doesn’t sound like “living” to me. But if we could figure out how caloric restriction works its magic, perhaps we could develop a drug that has the same effect without the discomfort.

That’s why this nematode work is important. Both genes contribute to metabolism. Reducing the expression of both simultaneously has a synergistic effect. I won’t get into the weeds here, but there’s a link to the paper in the IFLScience link below if you want more specificity. The key to pharmacology is having a druggable target, and this work suggests a couple of possibilities. So if you plan, like Woody Allen, to achieve immortality by not dying, watch this space!

https://www.iflscience.com/plants-and-animals/scientists-expand-the-lifespan-of-a-worm-by-500-percent-the-equivalent-of-four-centuries-in-humans/?fbclid=IwAR1hQkW4JJ8iWqlexO4BPAEKj1MoqTUYtL-ViblcSazFaTsyZ8raoMNlgBk