The effects of selection for larval behavior on adult life-history features in Drosophila melanogaster

Selection for late-life fecundity and longevity in adult Drosophila melanogaster is well known to modify numerous characteristics of life history and physiology. We report experiments here in which selection applied to behavior affects features in an identical fashion. Selection for feeding rate of larval D. melanogaster modifies caloric intake, as measured by the uptake and incorporation of labeled glucose. Selection for slow larval feeding produced lines of D. melanogaster in which larvae synthesized significantly less lipid prior to pupation and eclosed to have low early-life fecundity and a long life as adults. They also had greater lifetime fecundity, but lower viability of egg to hatched adult. Alternatively, fast-feeding larvae incorporated more lipid before pupation and eclosed with high early-fecundity that declined rapidly throughout their short adult life. Slow-feeding populations also had a significantly enhanced expression of the stress-resistance genes CuZn-SOD, CATALASE, and HSP70. Selection on larval feeding behavior reproduced the antagonistic evolutionary trade-off found under selection for adult life span and mimicked the physiological response in life span as seen in many species when dietary restriction is imposed on adults. Thus, nutrient acquisition during development appears to share a common evolutionary and genetic basis with the allocation processes that determine adult life-history traits and the related phenotypic dietary restriction phenomena.     

Compensatory ingestion upon dietary restriction in Drosophila melanogaster

Dietary restriction extends the lifespan of numerous, evolutionarily diverse species. In D. melanogaster, a prominent model for research on the interaction between nutrition and longevity, dietary restriction is typically based on medium dilution, with possible compensatory ingestion commonly being neglected. Possible problems with this approach are revealed by using a method for direct monitoring of D. melanogaster feeding behavior. This demonstrates that dietary restriction elicits robust compensatory changes in food consumption. As a result, the effect of medium dilution is overestimated and, in certain cases, even fully compensated for. Our results strongly indicate that feeding behavior and nutritional composition act concertedly to determine fly lifespan. Feeding behavior thus emerges as a central element in D. melanogaster aging.     

Autophagy is required for dietary restriction-mediated life span extension in C. elegans

Dietary restriction extends life span in diverse species including Caenorhabditis elegans. However, the downstream cellular targets regulated by dietary restriction are largely unknown. Autophagy, an evolutionary conserved lysosomal degradation pathway, is induced under starvation conditions and regulates life span in insulin signaling C. elegans mutants. We now report that two essential autophagy genes (bec-1 and Ce-atg7) are required for the longevity phenotype of the C. elegans dietary restriction mutant (eat-2(ad1113) animals. Thus, we propose that autophagy mediates the effect, not only of insulin signaling, but also of dietary restriction on the regulation of C. elegans life span. Since autophagy and longevity control are highly conserved from C. elegans to mammals, a similar role for autophagy in dietary restriction-mediated life span extension may also exist in mammals.     

Nutrients, not caloric restriction, extend lifespan in Queensland fruit flies (Bactrocera tryoni)

Caloric restriction (CR) has been widely accepted as a mechanism explaining increased lifespan (LS) in organisms subjected to dietary restriction (DR), but recent studies investigating the role of nutrients have challenged the role of CR in extending longevity. Fuelling this debate is the difficulty in experimentally disentangling CR and nutrient effects due to compensatory feeding (CF) behaviour. We quantified CF by measuring the volume of solution imbibed and determined how calories and nutrients influenced LS and fecundity in unmated females of the Queensland fruit fly, Bactocera tryoni (Diptera: Tephritidae). We restricted flies to one of 28 diets varying in carbohydrate:protein (C:P) ratios and concentrations. On imbalanced diets, flies overcame dietary dilutions, consuming similar caloric intakes for most dilutions. The response surface for LS revealed that increasing C:P ratio while keeping calories constant extended LS, with the maximum LS along C:P ratio of 21:1. In general, LS was reduced as caloric intake decreased. Lifetime egg production was maximized at a C:P ratio of 3:1. When given a choice of separate sucrose and yeast solutions, each at one of five concentrations (yielding 25 choice treatments), flies regulated their nutrient intake to match C:P ratio of 3:1. Our results (i) demonstrate that CF can overcome dietary dilutions; (ii) reveal difficulties with methods presenting fixed amounts of liquid diet; (iii) illustrate the need to measure intake to account for CF in DR studies and (iv) highlight nutrients rather than CR as a dominant influence on LS.     

Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster

The inability to properly balance energy intake and expenditure with nutrient supply forms the basis for some of today's most pressing health issues, including diabetes and obesity. Mechanisms of nutrient homeostasis may also lie at the root of dietary restriction, a manipulation whereby reduced nutrient availability extends lifespan and ameliorates age-related deteriorations in many species. The traditional belief that the most important aspect of the diet is its energetic (i.e. caloric) content is currently under scrutiny. Hypotheses that focus on diet composition and highlight more subtle characteristics are beginning to emerge. Using Drosophila melanogaster , we asked whether diet composition alone, independent of its caloric content, was sufficient to impact behavior, physiology, and lifespan. We found that providing flies with a yeast-rich diet produced lean, reproductively competent animals with reduced feeding rates. Excess dietary sugar, on the other hand, promoted obesity, which was magnified during aging. Addition of dietary yeast often limited or reversed the phenotypic changes associated with increased dietary sugar and vice versa, and dietary imbalance was associated with reduced lifespan. Our data reveal that diet composition, alone and in combination with overall caloric intake, modulates lifespan, consumption, and fat deposition in flies, and they provide a useful foundation for dissecting the underlying genetic mechanisms that link specific nutrients with important aspects of general health and longevity.     

Caloric restriction and the aging process: a critique

The main objective of this review is to provide an appraisal of the current status of the relationship between energy intake and the life span of animals. The concept that a reduction in food intake, or caloric restriction (CR), retards the aging process, delays the age-associated decline in physiological fitness, and extends the life span of organisms of diverse phylogenetic groups is one of the leading paradigms in gerontology. However, emerging evidence disputes some of the primary tenets of this conception. One disparity is that the CR-related increase in longevity is not universal and may not even be shared among different strains of the same species. A further misgiving is that the control animals, fed ad libitum (AL), become overweight and prone to early onset of diseases and death, and thus may not be the ideal control animals for studies concerned with comparisons of longevity. Reexamination of body weight and longevity data from a study involving over 60,000 mice and rats, conducted by a National Institute on Aging-sponsored project, suggests that CR-related increase in life span of specific genotypes is directly related to the gain in body weight under the AL feeding regimen. Additionally, CR in mammals and “dietary restriction” in organisms such as Drosophila are dissimilar phenomena, albeit they are often presented to be the very same. The latter involves a reduction in yeast rather than caloric intake, which is inconsistent with the notion of a common, conserved mechanism of CR action in different species. Although specific mechanisms by which CR affects longevity are not well understood, existing evidence supports the view that CR increases the life span of those particular genotypes that develop energy imbalance owing to AL feeding. In such groups, CR lowers body temperature, rate of metabolism, and oxidant production and retards the age-related pro-oxidizing shift in the redox state.     

Independent chemical regulation of health and senescent spans in Drosophila

Curcumin feeding of Drosophila larvae or young adults inhibits TOR and other known longevity genes and induces an extended health span in a normal-lived Ra strain adult. Combining larval curcumin feeding with an adult dietary restriction (DR) diet does not yield an additive effect. The age-specific mortality rate is decreased and is comparable with that of genetically selected long-lived La animals. Feeding Ra adults with the drug their whole life, or only during the senescent span, results in a weak negative effect on median longevity with no increase in maximum lifespan. The La strain shows no response to this DR mimetic. Thus, curcumin acts in a life stage-specific manner to extend the health span. Histone deacetylase inhibitors decrease the longevity of Ra animals if administered over the health span only or over the entire adult lifespan, but these inhibitors increase longevity when administered in the transition or senescent spans. Their major effect is a reduction in the mortality rate of older flies, raising the possibility of reducing frailty in older organisms. Their life stage-specific effects are complementary to that of curcumin. Use of stage-specific drugs may enable targeted increases in health or senescent spans, and thus selectively increase the quality of life.     

Nectarine promotes longevity in Drosophila melanogaster

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and health span. However, few fruits are known to improve the survival and health span in animals, let alone the underlying mechanisms. Here we investigate the effects of nectarine, a globally consumed fruit, on life span and health span in Drosophila melanogaster. Wild-type flies were fed standard, dietary restriction (DR), or high-fat diet supplemented with 0-4% nectarine extract. We measured life span, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-hydroxynonenal-protein adduct in these flies. We also measured life span, locomotor activity, and oxidative damage in sod1 mutant flies on the standard diet supplemented with 0-4% nectarine. Supplementation with 4% nectarine extended life span, increased fecundity, and decreased expression of some metabolic genes, including a key gluconeogenesis gene, PEPCK, and oxidative stress-response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR, or high-fat diet. Nectarine reduced oxidative damage in wild-type females fed the high-fat diet. Moreover, nectarine improved the survival of and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and health span partly by modulating glucose metabolism and reducing oxidative damage.     

Contributions of juvenile and adult diet to the lifetime reproductive success and lifespan of a spider

Food availability can vary widely for animals in nature and can have large effects on growth, reproduction and survival. While the consequences of food limitation for animals have been extensively studied, significant questions still remain including how ontogenetic variation in food availability contributes to lifetime reproductive success. We tested the effects of juvenile and adult food limitation on the lifetime reproductive success and lifespan of bridge spiders, Larinioides sclopetarius. Food availability was manipulated (low or high) over the entire juvenile and adult stage in a full‐factorial design and reproductive output and lifespan were measured. Juvenile and adult food limitation both reduced lifetime egg and hatchling production with effect sizes that were not significantly different from each other. Unlike some other arthropods, where juvenile food limitation reduces fecundity by reducing adult body size, body size was not affected by juvenile diet in bridge spiders. Clutch size was also significantly reduced by both juvenile and adult food limitation. The effect of adult diet on clutch size was stronger than that of juvenile diet. Juvenile and adult food limitation both extended total lifespan, and adult food limitation extended adult longevity (i.e. time from maturation to death). However, juvenile food limitation decreased adult longevity, in contrast to what would be predicted by dietary or caloric restriction. Compensatory feeding and growth are widely recognized mechanisms through which animals can ameliorate some of the negative effects of periods of food limitation. Yet our results combined with studies of a range of other species suggest that there may be lasting consequences of juvenile food limitation on lifetime reproductive success that cannot be compensated for by adult feeding in some species.     

An intervention resembling caloric restriction prolongs life span and retards aging in yeast.

The yeast Saccharomyces cerevisiae has a finite life span that is measured by the number of daughter cells an individual produces. The 20 genes known to determine yeast life span appear to function in more than one pathway, implicating a variety of physiological processes in yeast longevity. Less attention has been focused on environmental effects on yeast aging. We have examined the role that nutritional status plays in determining yeast life span. Reduction of the glucose concentration in the medium led to an increase in life span and to a delay in appearance of an aging phenotype. The increase in life span was the more extensive the lower the glucose levels. Life extension was also elicited by decreasing the amino acids content of the medium. This suggests that it is the decline in calories and not a particular nutrient that is responsible, in striking similarity to the effect on aging of caloric restriction in mammals. The caloric restriction effect did not require the induction of the retrograde response pathway, which signals the functional status of the mitochondrion and determines longevity. Furthermore, deletion of RTG3, a downstream mediator in this pathway, and caloric restriction had an additive effect, resulting in the largest increase (123%) in longevity described thus far in yeast. Thus, retrograde response and caloric restriction operate along distinct pathways in determining yeast longevity. These pathways may be exclusive, at least in part. This provides evidence for multiple mechanisms of metabolic control in yeast aging. Inasmuch as caloric restriction lowers blood glucose levels, this study raises the possibility that reduced glucose alters aging at the cellular level in mammals.     

Stochastic dietary restriction using a Markov-chain feeding protocol elicits complex, life history response in medflies

Lifespan in individually housed medflies (virgins of both sexes) and daily reproduction for females were studied following one of 12 dietary restriction (DR) treatments in which the availability of high-quality food (yeast-sugar mixture) for each fly was based on a Markov chain feeding scheme--a stochastic dietary regime which specifies that the future dietary state depends only on the present dietary state and not on the path by which the present state was achieved. The stochastic treatments consisted of a combination of one of four values of a 'discovery' parameter and one of three values of a 'persistence' parameter. The results supported the hypotheses that: (i) longevity is extended in most medfly cohorts subject to stochastic DR; and (ii) longevity is more affected by the patch discovery than the patch persistence parameter. One of the main conclusions of the study is that, in combination with the results of earlier dietary restriction studies on the medfly, the results reinforce the concept that the details of the dietary restriction protocols have a profound impact on the sign and magnitude of the longevity extension relative to ad libitum cohorts and that a deeper understanding of the effect of food restriction on longevity is not possible without an understanding of its effect on reproduction.     

Comparative and meta-analytic insights into life extension via dietary restriction

Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible.     

Having it all: historical energy intakes do not generate the anticipated trade-offs in fecundity

An axiom of life-history theory, and fundamental to our understanding of ageing, is that animals must trade-off their allocation of resources since energy and nutrients are limited. Therefore, animals cannot "have it all"--combine high rates of fecundity with extended lifespans. The idea of life-history trade-offs was recently challenged by the discovery that ageing may be governed by a small subset of molecular processes independent of fitness. We tested the "trade-off" and "having it all" theories by examining the fecundities of C57BL/6J mice placed onto four different dietary treatments that generated caloric intakes from -21 to +8.6% of controls. We predicted body fat would be deposited in relation to caloric intake. Excessive body fat is known to cause co-morbidities that shorten lifespan, while caloric restriction enhances somatic protection and increases longevity. The trade-off model predicts that increased fat would be tolerated because reproductive gain offsets shortened longevity, while animals on a restricted intake would sacrifice reproduction for lifespan extension. The responses of body fat to treatments followed our expectations, however, there was a negative relationship between reproductive performance (fecundity, litter mass) and historical intake/body fat. Our dietary restricted animals had lower protein oxidative damage and appeared able to combine life-history traits in a manner contrary to traditional expectations by having increased fecundity with the potential to have extended lifespans.     

The functional costs and benefits of dietary restriction in Drosophila

Dietary restriction (DR) extends lifespan in an impressively wide array of species spanning three eukaryotic kingdoms. In sharp contrast, relatively little is known about the effects of DR on functional senescence, with most of the work having been done on mice and rats. Here we used Drosophila melanogaster to test the assumption that lifespan extension through DR slows down age-related functional deterioration. Adult virgin females were kept on one of three diets, with sucrose and yeast concentrations ranging from 7% to 11% to 16% (w/v). Besides age-specific survival and fecundity, we measured starvation resistance, oxidative stress resistance, immunity, and cold-stress resilience at ages 1, 3, 5, and 7 weeks. We confirmed that DR extends lifespan: median lifespans ranged from 38 days (16% diet) to 46 days (11% diet) to 54 days (7% diet). We also confirmed that DR reduces fecundity, although the shortest-lived flies only had the highest fecundity when males were infrequently available. The most striking result was that DR initially increased starvation resistance, but strongly decreased starvation resistance later in life. Generally, the effects of DR varied across traits and were age dependent. We conclude that DR does not universally slow down functional deterioration in Drosophila. The effects of DR on physiological function might not be as evolutionarily conserved as its effect on lifespan. Given the age-specific effects of DR on functional state, imposing DR late in life might not provide the same functional benefits as when applied at early ages.     

Life history,ecology and longevity in bats

The evolutionary theory of aging predicts that life span should decrease in response to the amount of mortality caused by extrinsic sources. Using this prediction, we selected six life history and ecological factors to use in a comparative analysis of longevity among 64 bat species. On average, the maximum recorded life span of a bat is 3.5 times greater than a non-flying placental mammal of similar size. Records of individuals surviving more than 30 years in the wild now exist for five species. Univariate and multivariate analyses of species data, as well as of phylogenetically independent contrasts obtained using a supertree of Chiroptera, reveal that bat life span significantly increases with hibernation, body mass and occasional cave use, but decreases with reproductive rate and is not influenced by diet, colony size or the source of the record. These results are largely consistent with extrinsic mortality risk acting as a determinant of bat longevity. Nevertheless, the strong association between life span and both reproductive rate and hibernation also suggests that bat longevity is strongly influenced by seasonal allocation of non-renewable resources to reproduction. We speculate that hibernation may provide a natural example of caloric restriction, which is known to increase longevity in other mammals.     

Effects of the availability of food and water on reproduction in the African army worm, Spodoptera exempta

ABSTRACT. Female Spodoptera exempta (Walker) (Lepidoptera: Noctuidae) moths require access to water to achieve hydration and maturation of their oocytes if they are to achieve their potential fecundity. For moths provided with water, the main factor limiting fecundity is moth weight. There is some evidence that sucrose in the adult diet can increase fecundity, particularly in lighter moths from a suboptimal larval feeding regime. Moths fed sucrose live longer, but complete oviposition at about the same age as moths provided only with water. Dietary protein and amino acids have no effect on fecundity or longevity. Although- multiple matings are frequent in the laboratory, female S.exempta only need to mate once to complete oviposition. Differences are apparent in the relative contribution of larval and adult feeding to reproduction in Noctuidae. Some species, like S.exempta , require only water to achieve their reproductive potential, while others (e.g. Heliothis spp.) are dependent on sugars in the adult diet. Female S.exempta denied access to water or food until night 3 after eclosion and then provided with water or sucrose, commence oviposition on night 4 and have fecundities comparable with those moths fed from emergence.     

Calories do not explain extension of life span by dietary restriction in Drosophila

Dietary restriction (DR) extends life span in diverse organisms, including mammals, and common mechanisms may be at work. DR is often known as calorie restriction, because it has been suggested that reduction of calories, rather than of particular nutrients in the diet, mediates extension of life span in rodents. We here demonstrate that extension of life span by DR in Drosophila is not attributable to the reduction in calorie intake. Reduction of either dietary yeast or sugar can reduce mortality and extend life span, but by an amount that is unrelated to the calorie content of the food, and with yeast having a much greater effect per calorie than does sugar. Calorie intake is therefore not the key factor in the reduction of mortality rate by DR in this species.     

Autophagy is Required for Dietary Restriction-Mediated Life Span Extension in C. elegans

Dietary restriction extends life span in diverse species including Canorhabditis elegans. However, the downstream cellular targets regulated by dietary restriction are largely unknown. Autophagy, an evolutionary conserved lysosomal degradation pathway, is induced under starvation conditions and regulates life span in insulin signaling C. elegans mutants. We now report that two essential autophagy genes (bec-1 and Ce-atg7) are required for the longevity phenotype of the C. elegans dietary restriction mutant (eat-2ad1113) animals. Thus, we propose that autophagy mediates the effect, not only of insulin signaling, but also of dietary restriction on the regulation of C. elegans life span. Since autophagy and longevity control are highly conserved from C. elegans to mammals, a similar role for autophagy in dietary restriction-mediated life span extension may also exist in mammals.     

Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage

Many previous investigations have consistently reported that caloric restriction (40%), which increases maximum longevity, decreases mitochondrial reactive species (ROS) generation and oxidative damage to mitochondrial DNA (mtDNA) in laboratory rodents. These decreases take place in rat liver after only seven weeks of caloric restriction. Moreover, it has been found that seven weeks of 40% protein restriction, independently of caloric restriction, also decrease these two parameters, whereas they are not changed after seven weeks of 40% lipid restriction. This is interesting since it is known that protein restriction can extend longevity in rodents, whereas lipid restriction does not have such effect. However, before concluding that the ameliorating effects of caloric restriction on mitochondrial oxidative stress are due to restriction in protein intake, studies on the third energetic component of the diet, carbohydrates, are needed. In the present study, using semipurified diets, the carbohydrate ingestion of male Wistar rats was decreased by 40% below controls without changing the level of intake of the other dietary components. After seven weeks of treatment the liver mitochondria of the carbohydrate restricted animals did not show changes in the rate of mitochondrial ROS production, mitochondrial oxygen consumption or percent free radical leak with any substrate (complex I- or complex II-linked) studied. In agreement with this, the levels of oxidative damage in hepatic mtDNA and nuclear DNA were not modified in carbohydrate restricted animals. Oxidative damage in mtDNA was one order of magnitude higher than that in nuclear DNA in both dietary groups. These results, together with previous ones, discard lipids and carbohydrates, and indicate that the lowered ingestion of dietary proteins is responsible for the decrease in mitochondrial ROS production and oxidative damage in mtDNA that occurs during caloric restriction.     

Life history response of Mediterranean fruit flies to dietary restriction

The purpose of this study was to investigate medfly longevity and reproduction across a broad spectrum of diet restriction using a protocol similar to those applied in most rodent studies. Age-specific reproduction and age of death were monitored for 1200 adult males and 1200 females, each individually maintained on one of 12 diets from ad libitum to 30% of ad libitum. Diet was provided in a fixed volume of solution that was fully consumed each day, ensuring control of total nutrient consumption for every fly. Contrary to expectation and precedence, increased longevity was not observed at any level of diet restriction. Among females, reproduction continued across all diet levels despite the cost in terms of increased mortality. Among males, life expectancy exceeded that of females at most diet levels. However, in both sexes, mortality increased more sharply and the pattern of survival changed abruptly once the diet level fell to 50% of ad libitum or below, even though the energetic demands of egg production has no obvious counterpart in males. We believe that a more complete picture of the life table response to dietary restriction will emerge when studies are conducted on a wider range of species and include both sexes, more levels of diet, and the opportunity for mating and reproduction.