X-Message-Number: 26337 Date: Wed, 15 Jun 2005 17:34:27 -0700 (PDT) From: Doug Skrecky <> Subject: nuclear free radical theory of aging disproved [There is accumulating data indicating that free radicals have little or no effect on aging in "normal" long lived or wild type animals. In contrast short lived mutants often do suffer from diseases with a significant degree of free radical related pathology. A typical example of this would age and free radical related renal failure in Fisher 344 rats. The nucleus and mitochondria have been believed to the most important cellular sites of free radical damage. The present experiment largely eliminates the nucleus from further consideration, which I am sure will come as a shock to some (but not all) gerontologists. Mitochondria based theories of aging have run afoul from contradictory results as well. Hopefully this matter will be resolved soon. Until the impact (or lack thereof) of free radicals on aging is elucidated, other competing theories are likely to remain on the back burner.] Science. 2005 May 5; [Epub ahead of print] Extension of Murine Lifespan by Overexpression of Catalase Targeted to Mitochondria. To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). Median and maximum lifespans were maximally increased (average 5 months, and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=26337