Researcher Jan Vijg's profile at the Buck Institute for Age Research includes a link to the first chapter of his recent book, "Aging of the Genome" in PDF format. Vijg stands in the school that believes stochastic corruption of the genome is at the root of aging:
Instability of the genome has been considered as a possible cause of aging since the late 1940's, when it was discovered that low, daily doses of radiation accelerated symptoms of normal aging in rodents. A connection between damage to the genome and aging was strongly supported by the discovery that heritable defects in genome maintenance are associated with premature aging - as shown in Werner syndrome and Hutchinson Gilford Progeroid syndrome. The defects present in those conditions, and other defects, have been engineered in mice and shown to cause premature aging in these animals as well.
In the past, my laboratory has generated a transgenic mouse model harboring plasmids containing the bacterial lacZ gene. These plasmids can be recovered from genomic DNA and subsequently transferred into E. coli to positively select for colonies representing a mutant lacZ-plasmid. The ratio of colonies of lacZ mutants over lacZ wildtypes is a measure for the mutation frequency in the mouse. In this way we demonstrated that, as predicted, the frequency of mutations increases with age in most tissues and cell types. Our present work is focused on unraveling the mechanisms through which aging-related mutations are induced and obtaining insight as to how increased genomic instability can give rise to some of the most common aging-related phenotypes.
The contribution of random mutations in nuclear DNA to aging is up for debate, however. Aubrey de Grey, amonst others, argues that the rise in mutation rates over time - effectively damage to the operating instructions of cells - does not contribute meaningfully to the progression of aging, at least not in comparison to the other forms of biochemical damage that accumulate over time. Why worry about something that will cause issues when you're 200 if any one of a dozen other processes will finish you off long before that?
Both sides can marshall a decent argument; areas like this are usually where science is at its most interesting.
I'm not completely following along with the argument that progeria and Werner syndrome support the contribution of stochastic damage to the genome as a meaningful cause of aging. Both conditions seem to have very specific causes: mutation in Lamin A for progeria and something buried in the kinases for Werner syndrome. Similar issues are seen - to a much lesser degree - in the "normal" old. Does that mean that the contribution of stochastic mutations to degenerative aging is made by how often damage hits a couple of very important genes relating to structural integrity of the cell? That seems implausible given the rate of damage, the sheer number of genes and sheer number of cells involved. But perhaps damage is more likely to happen to structural genes than in other places; maybe stochastic mutation in the nucleus is not quite so stochastic as some might think.
Research continues, and we shall see.