Does the accumulation of DNA damage in the cellular nucleus contribute to significantly to aging? How, if so? It is a topic for debate, with a weight of papers behind many of the consensus interpretations, but most of the community would answer "yes" with some variety of qualifications. On the other side, biomedical gerontologist Aubrey de Grey argues that DNA damage - mutations to the DNA contained in the chromosomes - is not important over a normal human life span, except where it causes cancer:

we don't actually need to fix chromosomal mutations at all in order to stop them from killing us: all we need to do is develop a really really good cure for cancer.

Looking back in the Fight Aging! archives, you'll find plenty of theories on how DNA damage might contribute to degenerative aging. A short selection:

• Double strand breaks are the real problem
• Cancer stem cells arise from DNA damage
• DNA damage causes disarray in gene expression, which contibutes to aging
• DNA damage causes age-related reduction in stem cell capacity

And so forth - it isn't hard to find academic arguments for the role of DNA damage in most of the better known age-related degenerations. It's a matter of time, resources for research and scientific debate as to which pan out. Here's another different point of view from a recent paper, focusing on longevity genes and metabolic changes - such as those brought on by calorie restriction - that lead to greater longevity:

Age to survive: DNA damage and aging

Aging represents the progressive functional decline and increased mortality risk common to nearly all metazoans. Recent findings experimentally link DNA damage and organismal aging: longevity-regulating genetic pathways respond to the accumulation of DNA damage and other stress conditions and conversely influence the rate of damage accumulation and its impact for cancer and aging. This novel insight has emerged from studies on human progeroid diseases and mouse models that have deficient DNA repair pathways. Here we discuss a unified concept of an evolutionarily conserved 'survival' response that shifts the organism's resources from growth to maintenance as an adaptation to stresses, such as starvation and DNA damage. This shift protects the organism from cancer and promotes healthy aging.

It's a broad, interesting topic for study, I think you'll agree that much.

Posted by Reason at January 17, 2008 8:08 PM | TrackBack (0)