Sex and death in the mouse: genetically delayed reproduction and senescence

A mammalian model of genetically postponed aging would be an important tool to test not only different mechanisms of aging but also the predictive value of various biomarkers of the aging process. Under conventional conditions, the historical strains of the laboratory mouse produce their first litter between 9 and 13 weeks of age and have a median time of death in their 2nd year. Our POSCH-2 strain, which was derived from wild-caught Mus musculus domesticus, produces its first litter in the current breeding generations at approximately 47 weeks of age and continues to breed throughout its 2nd and into its 3rd year of life. The aging curve of POSCH-2 has not yet been determined for economic reasons. Late onset of breeding is a characteristic of both females and males, but sexual maturity is more reliably assessed in females. The later breeding phenotype of POSCH-2 is genetically recessive to early breeding of the C57BL/6J historical laboratory strain and, since POSCH-2 females can be induced to ovulate at 8 weeks of age (but pregnancy does not result), the signal rather than the ovarian receptor to ovulate may be delayed. The genetically delayed reproduction and potentially longer life of the POSCH-2 strain appears to be a new trait in the mouse. The strain may be a useful mammalian model for aging studies and for the evaluation of antagonistic pleiotropy as a genetic model for the evolution of aging.Key words: delayed reproduction, senescence, aging, genetics, mouse.

Quantitative genetics of postponed aging in Drosophila melanogaster. I. Analysis of outbred populations.

Selection has been used to create replicated outbred stocks of Drosophila melanogaster with increased longevity, increased later fecundity, and increased levels of physiological performance at later ages. The present study analyzed the quantitative transmission patterns of such stocks, employing extensive replication in numbers of stocks, individuals, and assayed characters. The populations used derived from five lines with postponed aging and five control lines, all created in 1980 from the same founding base population. The following characters were studied: early 24-hr fecundity, early ovary weight, early female starvation resistance, early male starvation resistance, female longevity and male longevity. Numerous crosses were performed to test for non-Mendelian inheritance, average dominance, maternal effects, sex-linkage and between-line heterogeneity. There was only slight evidence for any of these phenomena arising reproducibly in the characters studied. These findings suggest the value of this set of stocks for studies of the physiological basis of postponed aging.

Quantitative genetics of postponed aging in Drosophila melanogaster. II. Analysis of selected lines.

Quantitative genetic analyses of Drosophila melanogaster stocks with postponed aging have suffered from the problem of a lack of certainty concerning patterns of allelic differentiation. The present experiments were designed to alleviate this difficulty by selecting for enhanced levels of characters known to be related to postponed aging. Selection successfully increased the degree of differentiation of postponed aging stocks with respect to starvation resistance and fecundity, but persistent additive genetic variance suggested that selection did not result in fixation of alleles. The artificially selected stocks were subjected to crosses to test for patterns of dominance and maternal effects. There was little evidence for these effects in the inheritance of the characters underlying postponed aging, even with the increased differentiation of the selected stocks.