Roaches, apoptosis and the ovarian clock: use it or lose it

Abstract

F or many female animals, including humans, aging is accompanied by declines in reproductive success. Fecundity declines are often attributed to a loss of ovulatory capacity, either due to depletion of finite stores of ovarian follicles or loss of ability to generate viable eggs. In the view of evolutionary senescence and life-history theory, reproductive aging is an expected result of genetic and physiological trade-offs between investment in reproduction and long-term somatic maintenance, and of weakened natural selection on older organisms (Kirkwood and Austad, 2000). Nutritional interventions, such as food restriction, have been shown to affect aging and reproductive lifespan in a wide variety of invertebrate and vertebrate species, and experimental manipulation of the timing and rate of reproduction often have a robust influence on aging and longevity (Partridge et al., 2005). But relatively little research has focused on how altered nutrition and reproduction early in the life span affect specific physiological or cellular changes correlated with ovarian senescence and female reproductive failure. In an intriguing new study, Edvardsson et al. (2009) estimated quantitative genetic variation in the regulation of aging-related rates of ovarian apoptosis (a measure of ovarian senescence) under both severe food restriction and ad lib feeding in the African cockroach, Nauphoeta cinerea (Figure 1). It is important to note that they found rates of ovarian apoptosis to be almost fourfold higher in food-deprived than ad lib-fed females. In addition, they report reductions in female reproductive lifespan and increased rates of ovarian apoptosis after food restriction (but not food excess) when combined with experimentally delayed first reproduction. Their results suggest that, at least under certain environmental circumstances, this cellular correlate of infertility is under additive genetic control, and hence is subject to natural selection. Previous work by members of this group reported that loss of fertility in female cockroaches forced them to delay their first mating after sexual maturity, which is associated with higher rates of oocyte loss through apoptosis throughout the reproductive life span, effectively forcing females to adopt a ‘use it or lose it’ strategy (Moore and Sharma, 2005). In sexually reproducing animals, the balance between the rates of mitosis and apoptosis (programmed cell death) is continuously shifting during the healthy lifespan of an organism, including the developmental period (Hussein, 2005). During ovarian development and sexual maturation, coordinated waves of apoptosis set the stage for healthy oogenesis and staging of preovulatory follicles. As the ovary ages, higher rates of apoptosis are a benchmark of impending infertility. But why study ovarian aging in cockroaches in the first place? Nauphoeta arguably is a much less popular laboratory animal than its distant insect relative, the fruit fly Drosophila melanogaster, the classical model for genetic studies and endocrinological basis of trade-offs between fecundity and longevity. Moreover, our molecular toolkit for understanding basic aging processes in invertebrates is far better developed in both Drosophila and the nematode, Caenorhabditis elegans. But cockroaches have established—if relatively unsung—utility for studies of basic neuroendocrinology and reproduction. Even more important from a comparative aging standpoint, insects exhibit immense diversity in their reproductive biology that may or may not be reflected in differences in the proximate mechanisms underlying reproductive trade-offs. While Drosophila is a marvelous genetic model for studies of reproductive trade-offs, unlike vertebrates and many other animals, fruit flies are oviparous, with ovaries that continuously generate new oogonia and viable new eggs over the course of the normal reproductive life span. Nauphoeta, in contrast, is ovoviviparous, and bears live offspring. ‘Pregnant’ female roaches carry embryos in a brood pouch until they reach the firstinstar stage. Rather than reproducing continuously, they exhibit cycles of oocyte maturation followed by this specialized form of parental care. In this and previous studies by Moore and Moore (2001), delays in first reproduction combined with severe food deprivation reduced female roaches’ lifetime reproductive success and induced early infertility. In a general sense, these findings parallel the results of a plethora of food restriction studies from the aging literature. In the lexicon of biogerontology, however, ‘food restriction’ usually is not equated with complete food deprivation, as in the cockroach study. Instead, it usually entails a significant caloric restriction of 20–30% of normal ad lib food intake without actual starvation or malnourishment, and with adjustments in essential micronutrients to compensate for reduced food intake. In Drosophila and many other animal species, less