X-Message-Number: 13373 Date: Wed, 8 Mar 2000 01:04:41 -0800 (PST) From: Doug Skrecky <> Subject: mitochondrial theory of aging Citations: 1-2 <1> Authors Gershon D. Institution Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel. Title The mitochondrial theory of aging: is the culprit a faulty disposal system rather than indigenous mitochondrial alterations? [comment]. [Review] [16 refs] Comments Comment on: Exp Gerontol 1999 Aug;34(5):605-12 Source Experimental Gerontology. 34(5):613-9, 1999 Aug. Abstract Mitochondrial damage and the proportion of effete mitochondria in cells increase with age. According to the mitochondrial theory of aging, this phenomenon is mostly due to oxidative damage and is a major (and, some argue, the main) determinant of aging. It will be argued briefly that this phenomenon plays a role that is not exclusively crucial in aging. It will also be contended, essentially on theoretical grounds (for lack of sufficient current information), that there is low probability that the accumulation of reduced degradation of affected mitochondria is due to diminished production of hydroxyl radicals, as suggested by Aubrey and de Grey (1997) and expanded by Kowald (in this issue). What seems more likely is that the phagolysosomal disposal system of effete mitochondria is considerably altered in cells of aging organisms. Also, in view of the significant role of damaged mitochondria in the initial steps in apoptosis and the lack of evidence of massive apoptosis of cells in senescent individuals, the damage that exists may be milder than anticipated by the mitochondrial theory of aging. A brief fundamental summary on the biology of mitochondria is included for the sake of better understanding the arguments presented in this article. Also, suggestions are made for experimental testing of the hypotheses presented by Aubrey and de Grey (1997) and Kowald (1999). [References: 16] <2> Authors Kowald A. Institution Innovationskolleg Theoretische Biologie, Humboldt University Berlin, Germany. Title The mitochondrial theory of aging: do damaged mitochondria accumulate by delayed degradation? [see comments]. [Review] [42 refs] Comments Comment in: Exp Gerontol 1999 Aug;34(5):613-9 Source Experimental Gerontology. 34(5):605-12, 1999 Aug. Abstract The mitochondrial theory of aging states that the slow accumulation of impaired mitochondria is the driving force of the aging process. In recent years, this theory has gained new support with the discovery of age-related mitochondrial DNA deletions. However, the underlying mechanism of the accumulation of defective mitochondria remained unclear. This has changed recently with the proposal of de Grey that damaged mitochondria have a decreased degradation rate. The resulting increase in biological half-life would be a strong selection advantage leading to the accumulation of defective mitochondria. In this article, I summarize current ideas on how damaged organelles can build up in a cell as well as the shortcomings of these ideas. Then the new hypothesis and its justification are described. It appears that de Grey's hypothesis is a very promising concept that elegantly solves inconsistencies of current models and is in accordance with experimental findings. [References: 42] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=13373