Researchers at the Harvard Medical School will be publishing details in the November 28 edition of Cell of a potential mechanism of aging that is conserved throughout the animal kingdom, from yeast to humans.

Professor David Sinclair and his team have discovered that aging may in fact be a case of gene regulation gone haywire, as our cells progressively lose their ability to maintain accurate gene expression patterns.

What this means is, while every cell in our body could potentially express genes from any other cell in our body; e.g., a retina cell could start behaving like a kidney cell, it doesn’t because tissue patterns of gene expression are kept under tight control. And well they should – a lot of damage would result if our brain started releasing digestive enzymes.

However, as we age, cells lose this ability and start behaving in a sloppy and erratic way – a lot like old people themselves! These haplessly activated genes are directly linked with the characteristics of aging.

Under normal conditions, sirtuins (those enzymes activated by resveratrol and caloric restriction) police the situation, making sure that the extraneous DNA that is supposed to remain silent and wrapped up actually does so. However, sirtuins have a dual role – when DNA is damaged by UV light or free radicals, sirtuins act as volunteer emergency responders. They leave their genomic guardian posts and aid the DNA repair mechanism at the site of damage.

During this period of distraction, the epigenetic packaging of the genome starts to come apart and the wrong genes start to be expressed. The more DNA damage and free radical activity that occurs (especially due to age-related mitochondrial decay), the more time the sirtuins are deployed elsewhere, and the more time the cell spends doing the wrong, harmful thing.

So, intuitively the solution would be to increase sirtuin number/activity, and this is what CR dieters and resveratrol supplementers are attempting. Sirtuin-overexpressing mice (either as a result of germ-line genetic alteration or resveratrol supplementation) saw a mean lifespan increase of 24-46 percent.

This also lends weight to anti-free radical therapies and mitochondria-preserving therapies (e.g. ALCAR+r-ALA supplementation) as relevant adjuvants to sirtuin stimulation.

This proof-of-concept sure has me hankering for the 2nd generation sirtuin enhancers like SRT-1720 set to hit the markets in the next couple of years. In the meantime, it’s really some excellent food for thought. Could this actually be the root cause of aging in all organisms?

Adapted from a Eurekalert! press release. Photo credit: Cliff1066/flickr