Aging Aging

8 Strehlerdria obtained from animals of different ages. We found no differences betweenmitochondria from 8-mo-old rat hearts and 24-mo-old rat hearts, using α-ketoglutaricacid as substrate. Later it was reported that some mitochondria fromold animals oxidize different substrates such as succinate less efficiently thando mitochondria derived from young animals. Later in this book Miquel et al.summarize the literature, including much of their own work, on various morphologicaland functional changes that accumulate with age in mitochondria.These changes are thought to result from an accumulation of various types ofmutations in the mitochondrial genome (much of which codes for polypeptidesinvolved in Complex I and II of the respiratory redox chain) that result fromprimarily reactive oxygen species damage to the mitochondrial genome that ispoorly, if at all, repaired. Turnbull et al. present two chapters later in this bookon the analysis of mitochondrial DNA mutations. Such an age-related decreasein mitochondrial function has been proposed to lead to the bioenergetic declineof cells and tissues and so contribute to the aging process (27).4. Is a limitation in the number of divisions a body cell can undergo (in cellculture) a significant cause of aging?Alexis Carrel reported (3) that he was able to keep an embryonic chickenheart alive for more than 22 yr. This is, of course, much longer than chickensusually live and Carrel concluded that regular supplements of the growth mediumwith embryo extracts would keep these cultures alive for very long times,perhaps indefinitely. To quote from p. 173 of the Carrel book, “If by an appropriatetechnique, their volume is prevented from increasing, they never growold.” Colonies obtained from a heart fragment removed in January 1912, froma chick embryo, are growing as actively today as 23 yr ago. In fact, are theyimmortal? Maybe so. For many individuals, including myself at about 13 yr ofage, these findings were very exciting. Perhaps man would eventually be ableto conquer his oldest enemy, aging. It was at about that time that I decided on acareer in aging research.In 1965 my good friend Leonard Hayflick reported some research he and acolleague (Moorhouse) had carried out that appeared to be contrary to what therenaissance man, Carrel, had concluded (28). Hayflick found that human fibroblastsin a culture medium could go through only about 50 doublings, afterwhich the cells died or stopped dividing (now known as replicative senescence)or both. Hayflick’s data have been confirmed by many persons, including thisauthor, who with Robert Hay (29) carried out similar experiments on chickenfibroblasts that were only capable of about 20 doublings. However, because anew layer of skin cells is produced about every 4 d (about 90 doublings per yrand 9000 doublings in a 100-yr lifetime), and because red blood cells are producedby the millions every 120 d and because the crypt cells in the lining of