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Targeted mutation of the p66 gene, in mice, results in reduced oxidative stress, increased metabolic rate and in an increase in lifespan associated to a delayed aging without any apparent “side effect”. The antagonistic pleiotropy theory of aging predicts that for each immediate benefit there is a price to pay later in life, for example a negative correlation between longevity and reproductive success has been reported. Main aim of this study was to investigate whether the increased lifespan in the p66 mice has a cost in terms of their overall fitness. To this purpose we looked at repeated breeding cycles, breeding under stressful conditions, mean number of pups per nest and time of the onset of puberty. Since p66 mice are characterized by a decreased emotionality we also investigated whether this characteristic may be mediated by changes in early environmental factors, such as maternal care. To this purpose, we tested the effects of the p66 deletion on maternal behavior from postnatal day 1 to 8. P66 mice showed an overall earlier onset of puberty in addition to a reduced fertility both over repeated breeding cycles and under challenging stressful situations; mean number of pups did not differ between the two genotypes. A redirection of maternal behavior was observed in mutant mice as a function of their feeding pattern, which might account for the anticipated onset puberty observed in the offspring. Taken together our results show that p66 is important for optimal reproductive success. The lack of the gene is able to affect sexual maturation, an effect possibly mediated by changes in maternal care.

Delayed aging has a cost: reduced fertility, redirection of maternal activities and earlier onset of puberty in p66Shc-/- mice