A great deal of data is being generated on patterns of DNA methylation, aging, and variations in human longevity: "(1) we evaluated the DNA methylation from peripheral leukocytes of 21 female centenarians, their 21 female offspring, 21 offspring of both non-long-lived parents, and 21 young women ... (2) we compared the DNA methylation profiles of these populations ... We observed an age-related decrease in global DNA methylation and a delay of this process in centenarians' offspring. Interestingly, literature data suggest a link between the loss of DNA methylation observed during aging and the development of age-associated diseases. Genome-wide methylation analysis evidenced DNA methylation profiles specific for aging and longevity: (1) aging-associated DNA hypermethylation occurs predominantly in genes involved in the development of anatomical structures, organs, and multicellular organisms and in the regulation of transcription; (2) genes involved in nucleotide biosynthesis, metabolism, and control of signal transmission are differently methylated between centenarians' offspring and offspring of both non-long-lived parents, hypothesizing a role for these genes in human longevity. Our results suggest that a better preservation of DNA methylation status, a slower cell growing/metabolism, and a better control in signal transmission through epigenetic mechanisms may be involved in the process of human longevity. These data fit well with the observations related to the beneficial effects of mild hypothyroidism and insulin-like growth factor I system impairment on the modulation of human lifespan."
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Epigenetic changes may be programmed to pace the tempo of development and aging -
progressing 20 times faster in mice than in long-lived humans:
"Biological Significance of DNA Methylation in the Ageing Process"
http://ageing.oxfordjournals.org/content/22/suppl_1/S34.abstract
Caloric restriction may slow epigenetic changes:
http://www.ncbi.nlm.nih.gov/pubmed/7680421
And, epigenetic changes are non-random, patterned and tissue and age specific
http://www.impactaging.com/papers/v3/n10/full/100395.html
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014821
It seems worth considering that these changes are orchestrated by a genetic program rather than metabolic collateral damage.