On several occasions both in this blog and in my treatise I have pointed out the need for integrating the various disparate theories of aging into an overall systems framework. Following is the abstract for a presentation I will be offering at the American Aging Association’s 39th Annual Meeting and 24th Annual Meeting of the American College of Clinical Gerontology in Portland Oregon June 4-7, 2010:
Towards a systems view of aging
A comprehensive systems theory of aging must embrace the validated teachings of multiple existing special theories of aging, theories that range from oxidative damage to loss of mitochondrial function to neurological degeneration to telomere shortening and cell senescence to decline in hormone levels. The author has characterized 14 such major theories and an additional 7 candidate ones. While each such theory is correct in its own framework of reference, on the surface most seem to be largely independent of the others. However, on the levels of molecular biology and genomics a rich network of links exists among these theories. The author suggests two overarching frameworks for integrating and clarifying existing understandings from the diverse theories of aging. One framework is lifelong programmed changes in global gene expression due to DNA methylation, histone acetylation and other epigenomic modifications. For example, aging-related decline of efficacy of DNA repair machinery might possibly result from promoter methylation of the Mms22 gene, resulting in increasing susceptibility to oxidative damage with age. Promoter methylation of the P21 and P53 apoptosis genes can result in increased susceptibility to cancers. The second framework sees aging as decline in functioning of the stem cell supply chain, the chain where adult stem and progenitor cells progressively differentiate as-needed into other cells of increased specificity and decreased pluripotency, resulting in lifelong renewal of somatic cell types. As the supplies of multipotent mesenchymal and haemopoietic stem cells available in their niches for differentiation decline because of their replicative senescence, for example, fewer progenitor and somatic cells are available to replace ones that have died or become senescent. The paper will embody insights developed over a multi-year period and described in the author’s online treatise ANTI-AGING FIREWALLS – THE SCIENCE AND TECHNOLOGY OF LONGEVITY and in the hundreds of postings in the author’s blog www.anti-agingfirewalls.com.
In the course of the next couple of weeks I expect to produce a more detailed version of that presentation for this blog.
Vincent , have you seen this article? http://www.telegraph.co.uk/health/healthnews/7701065/Seventeen-year-old-locked-in-toddlers-body-could-unlock-key-to-ageing.html
I did look at the article. It is a very strange case of physical development arrest. Study of this case may tell us something about early-stage aging as related to development but my guess is that it is unlikely to tell us much about post-maturity aging or how lives may be extended. The obvious point is that there is an aging program that starts with conception. Verious bugs in the aging program can impede normal development to maturity, as in the case of the boy described in the article. While many researchers do not think there is an aging program that continues after maturity, several including myself think that in effect there is one or several. In my treatise I have discussed two frameworks for such a program, Programmed Epigenomic Changes and Stem Cell Supply Chain Breakdown.