X-Message-Number: 26230 From: "mike99" <> Subject: Fwd: Mice offspring of older moms die younger Date: Mon, 23 May 2005 16:16:30 -0600 From: "Robert J. Bradbury" <> Date: Fri, 20 May 2005 17:39:33 -0700 (PDT) To: Gerontology Research Group <> Subject: [GRG] Longevity decrease in children of elderly parents. Reply-To: Gerontology Research Group <> I'm sure Leonid will be interested in this. Stan and others involved in the supercentenarian research might be as well. Scienceblog is reporting: "Mice offspring of older moms die younger". http://www.scienceblog.com/cms/node/7954 This is consistent with my "Grand Unified Theory of Aging" that no matter how you slice it genome mutations due to double strand break repair (actually mis-repair) gradually corrupt the genomes of individual cells. The longer a cell has been around the more likely it is to contain errors. (Major errors show up as decreased fertility or miscarriages; minor errors show up in the decreased longevity of ones offspring.) On this point Aubrey and I are in rather sharp disagreement. Speaking to his specific point of "Chromosomal mutations and how to obviate them" [1]. I believe that he underplays the significance. If the genomic mutations are accumulating in the germ cells then this obviously has a health-span impact upon ones children (as cited above). What is less clear is precisely what the negative impact of individual nuclear (genomic) DNA mutations is within each cell which do not happen to mutate with tumor suppressor genes or oncogenes (which are perhaps only 2-5% of the potential targets in the genome -- depending upon how many genes are active in a particular cell type)? I.e. if you are *not* mutating tumor suppressor genes or oncogenes you *are* mutating other genes -- *some* of which are essential for the robust performance of the cell within whatever niche it occupies within the body. E.g. Neurons do not normally replicate and so cancer is hard to induce in neurons. But day-in and day-out they may be subjected to genome altering nuclear DNA mutations. The same is true for both eggs (where there is some open question with regard to whether or not precursors are available and the extent to which they replicate) and sperm (where the precursors obviously replicate but we may not have a clear picture with respect to what kind of selection is taking place to eliminate those with significantly defective genomes). My suggestion would be to come around full circle... If viable organisms are dependent upon trillions of cells with "functional" genomes and reproduction is dependent upon two "functional" genomes that happen to connect we really need a better picture of how much (and at what rates) damage accumulates that make either survival or reproduction extremely doubtful activities. Robert 1. http://www.gen.cam.ac.uk/sens/cancer.htm Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=26230