Why are babies young? Meiosis may prevent aging of the germ line.

Abstract

WHY ARE BABIES YOUNG? MEIOSIS MAY PREVENT AGING OF THE GERM LINE CAROL BERNSTEIN* The aging of a multicellular organism seems to have at least three components. One of these is irreversible damage to functional structures , such as bacterial decay of teeth and the pitting and eroding of articular surfaces where bones contact each other. This is a "wear and tear" component that is not compensated for by available repair mechanisms. Strehler [1] has described some of these processes. A second component is programmed alterations, such as the hormonecontrolled declining mass of bone in men and women with increasing age [I]. Further evidence for programmed contributions to aging, from the brain-endocrine system, is reviewed by Timiras [2]. A third component of aging is the accumulation of lesions in DNA which lead to loss of cell function. Evidence for this component is summarized by Hart [3]. One of his examples is the increasing proportion of defective proteins synthesized with increasing age, which apparently reflects loss of DNA information content. Another is the observation that agents which damage DNA have the uniform effect of shortening the life span of cells in vitro. When a new organism arises from a single fertilized egg cell, the first two components of aging are removed. There are no damaged structures and the developmental program is reinitiated at the beginning. Lesions in the germ line DNA, however, are not removed by merely starting with a single cell. Germ line DNA lesions are probably avoided or reduced in a number of ways. For instance, the usual extraperitoneal location of the testes in mammals has been calculated [4] to result in a twofold reduction in the heat-induced contribution to the spontaneous mutation rate in male germinal tissues. ?Molecular Biology Program, Department of Microbiology, College of Medicine, University of Arizona, Tucson, Arizona 85724. I would like to thank Harris Bernstein, Helen Gensler, and Scott McGirr for stimulating discussions while this article was being written. Some of the work on which these ideas were based was supported by Grant PCM 77-14971 from the National Science Foundation.© 1979 by The University of Chicago. 003 1-5982/79/2204-0095$01.00 Perspectives in Biology and Medicine ¦ Summer 1979 ] 539 It would also clearly be advantageous for an organism to maximize the repair of DNA lesions in the germ line and, thus, remove this source of aging to the greatest possible extent. There is accumulating evidence that this function is served by meiosis and particularly by DNA repair events that occur during the intimate pairing of chromosomes associated with this process. However, the primary evidence for repair processes depending on close association of DNA molecules comes not from higher organisms but from procaryotes. In bacteria and bacteriophages, some major repair modes become available only when homologous chromosomes are allowed to interact intimately. An efficient form of repair for many kinds of lesions in bacteriophage T4, called multiplicity reactivation, is thought to occur by such an intimate interactive process. Multiplicity reactivation has been shown to be important for overcoming lesions induced by ultraviolet (UV) light [5, 6], X-rays [7, 8], 32P decay [9], nitrous acid [10], N-methyl-N'-nitro-N-nitrosoguanidine [11], and ethyl methanesulfonate [12]. There is apparently more than one mechanism of multiplicity reactivation in bacteriophage T4. For UVlight - and nitrous acid-induced lesions, it depends on certain enzymes essential for recombination [10], while for lesions induced by Nmethyl -N'-nitro-N-nitrosoguanidine and ethyl methanesulfonate it does not depend on these enzymes [11, 12]. Repair processes depending on the interaction of homologous chromosomes have also been shown to be important for UV-light-induced lesions of bacteriophage ? [13, 14], for nitrogen mustard- or UV-light-induced lesions of bacteriophage P22 [15], and for repair of double-strand breaks in£. coli [16]. Such a repair process has also been suggested as the basis ofthe high radioresistance of Micrococcus radiodurans, since it always has multiple chromosomes present [17]. If repair is substantially promoted by the intimate pairing of chromosomes , then, for cells undergoing meiosis, the greatest sensitivity to lethal agents should occur after the pairing of extended chromosomes is over. Eriksson and Tavrin [18] have summarized the meiotic...