Investigations on the nature of the cost of reproduction: susceptibility to heat stress in fruitflies.

Studies in various species have shown that changes in reproductive activity result in inverse changes in life span. It is interesting to know how this "cost of reproduction" is incurred. It is possible that reproductive activity renders the organism more vulnerable to stress and that accumulated damage has a role in the observed decrease in life span. Previously, other investigators had shown that mated female fruitflies have significantly shorter life spans than virgin females. We compare mated and virgin young fruitflies for susceptibility to lethal heat stress. Preliminary results suggest that mated fruitflies are significantly more susceptible to heat stress than virgin ones.

An appetite for death.

A diverse array of organisms live longer under dietary restriction. Here, a hypothesis is proposed as a framework for interpreting this phenomenon. Dietary restriction is explained in terms of evolution and antagonistic pleiotropy. Focusing on the decline in reproductive capacity seen in dietary restriction, it is submitted that "normal" appetite is geared toward producing a neuroendocrine and metabolic internal milieu optimized for reproduction, with long-term detrimental effects on health as a by-product. In dietary restriction experiments, the animal is prevented from eating enough to attain this internal milieu and, as a by-product, lives longer.

Reproductive switch and aging: the case of leptin change in dietary restriction.

We have proposed that normal food intake is geared toward optimizing the internal milieu for reproduction, despite some components of this milieu being detrimental to health. In dietary restriction, the animal is prevented from eating enough to attain or maintain reproductive capacity and this particular milieu does not materialize. Life extension occurs as a by-product. This idea provides a framework for exploring biomolecular changes in dietary restriction and their relevance to aging. Leptin is a case in point: here, a decrease in leptin level in dietary restriction is explored in the light of leptin's role in the complex signaling system of reproductive switch.

Apolipoprotein E genotype and age at menopause.

We tested the hypothesis that there is a connection between apolipoprotein E (APOE) genotype and age at menopause. A sample of women aged between 50 and 60 years who had reached natural menopause was studied. Survival analysis of data showed a significant relationship between APOE genotype and age at menopause, carriers of the APOE4 allele reaching menopause at an earlier age. Our findings can have a bearing on the question of the evolution of this major human polymorphism and human life history. These findings are also relevant to the question of the connection between reproductive parameters and age-associated diseases.