Inter-tissue communication of mitochondrial stress in aging.

The protein homeostasis in mitochondria is critical for the normal physiological function of cells. To cope with mitochondrial stress, cells elicit specific stress response named mitochondrial unfolded protein response (UPRmt), to maintain mitochondrial homeostasis and repair mitochondrial function. Although severe damage to mitochondria is detrimental, studies in worms, flies, and mice have shown that mild mitochondrial damage promotes longevity by activating UPRmt. Interestingly, UPRmt can also be induced in a cell non-autonomous manner in cells or tissues which are not directly experiencing mitochondrial stress. The secreted molecules called "mitokine" are responsible for the mitochondrial stress communication between different tissues. This inter-tissue regulation of mitochondrial stress response systematically coordinates the adaptation ability which is closely associated with aging and a variety of diseases such as neurodegeneration and cancer. In this review, we summarize recent advances about inter-tissue mitochondrial stress communications, and introduce the current knowledge about the "mitokine" and its regulation on aging for further studies.

FPR1 is essential for rapamycin-induced lifespan extension in Saccharomyces cerevisiae.

FK506-sensitive proline rotamase 1 protein (Fpr1p), which is a homologue of the mammalian prolyl isomerase FK506-binding protein of 12 kDa (FKBP12), is known to play important roles in protein folding and prevention of protein aggregation. Although rapamycin is known to bind to Fpr1p to inhibit Tor1p mediated-mechanistic Target Of Rapamycin (mTOR) activity, the physiological functions of Fpr1p on lifespan remain unclear. In this study, we used the eukaryotic model Saccharomyces cerevisiae to demonstrate that deletion of FPR1 reduced yeast chronological lifespan (CLS), and there was no benefit on lifespan upon rapamycin treatment, indicating that lifespan extension mechanism of rapamycin in yeast is exclusively dependent on FPR1. Furthermore, there was a significant increase in CLS of fpr1Δ cells during caloric restriction (CR), suggesting that rapamycin affects lifespan in a different way compared to CR. This study highlights the importance of FPR1 for rapamycin-induced lifespan extension.

Whole organism aging: Parabiosis, inflammaging, epigenetics, and peripheral and central aging clocks. The ARS of aging.

The strong interest shown in the study of the causes of aging in recent decades has uncovered many mechanisms that could contribute to the rate of aging. These include mitochondrial ROS production, DNA modification and repair, lipid peroxidation-induced membrane fatty acid unsaturation, autophagy, telomere shortening rate, apoptosis, proteostasis, senescent cells, and most likely there are many others waiting to be discovered. However, all these well-known mechanisms work only or mainly at the cellular level. Although it is known that organs within a single individual do not age at exactly the same rate, there is a well-defined species longevity. Therefore, loose coordination of aging rate among the different cells and tissues is needed to ensure species lifespan. In this article we focus on less known extracellular, systemic, and whole organism level mechanisms that could loosely coordinate aging of the whole individual to keep it within the margins of its species longevity. We discuss heterochronic parabiosis experiments, systemic factors distributed through the vascular system like DAMPs, mitochondrial DNA and its fragments, TF-like vascular proteins, and inflammaging, as well as epigenetic and proposed aging clocks situated at different levels of organization from individual cells to the brain. These interorgan systems can help to determine species longevity as a further adaptation to the ecosystem.

Physical fitness, cognition, and structural network efficiency of brain connections across the lifespan.

Inadequate levels of exercise is one of the most potent modifiable risk factors for preventing cognitive decline and dementia as we age. Meanwhile, network science-based measures of structural brain network global and local efficiency show promise as robust biomarkers of aging, cognitive decline, and pathological disease progression. Despite this, little to no work has established how maintaining physical activity (PA) and physical fitness might relate to cognition and network efficiency measures across the lifespan. Therefore the purpose of this study was to determine the relationship between (1) PA and fitness and cognition, (2) fitness and network efficiency, and (3) how network efficiency measures relate to cognition. To accomplish this, we analyzed a large cross-sectional data set (n = 720; 36-100 years) from the aging human connectome project, which included the Trail Making Task (TMT) A and B, a measure of fitness (2-min walk test), physical activity (International Physical Activity Questionnaire), and high-resolution diffusion imaging data. Our analysis consisted of employing multiple linear regression while controlling for age, sex, and education. Age was associated with lower global and local brain network efficiency and poorer Trail A & B performance. Meanwhile, fitness, but not physical activity, was related to better Trail A and B performance and fitness, and was positively associated with local and global brain efficiency. Finally, local efficiency was related to better TMT B performance and partially mediated the relationship between fitness and TMT B performance. These results indicate aging may be associated with a shift towards less efficient local and global neural networks and that maintaining physical fitness might protect against age-related cognitive performance deterioration by bolstering structural network efficiency.

Knockdown of phosphatases of regenerating liver-1 prolongs the lifespan of Caenorhabditis elegans via activating DAF-16/FOXO.

Phosphatases of regenerating liver (PRLs) are dual-specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C. elegans). Structurally, this phosphatase in C. elegans, named PRL-1, consisted of a conserved signature sequence WPD loop and a single C(X)5 R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL-1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding-based RNA-interference method, knockdown of prl-1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl-1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin-like growth factor 1 signaling pathway, and SIR-2.1 but through a DAF-16-dependent pathway. Moreover, knockdown of prl-1 induced the nuclear translocation of DAF-16, and upregulated the expression of daf-16, sod-3, mtl-1, and ctl-2. Finally, suppression of prl-1 also reduced the ROS. In conclusion, suppression of prl-1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases.

Longitudinal telomere dynamics within natural lifespans of a wild bird.

Telomeres, the nucleotide sequences that protect the ends of eukaryotic chromosomes, shorten with each cell division and telomere loss may be influenced by environmental factors. Telomere length (TL) decreases with age in several species, but little is known about the sources of genetic and environmental variation in the change in TL (∆TL) in wild animals. In this study, we tracked changes in TL throughout the natural lifespan (from a few months to almost 9 years) of free-living house sparrows (Passer domesticus) in two different island populations. TL was measured in nestlings and subsequently up to four times during their lifetime. TL generally decreased with age (senescence), but we also observed instances of telomere lengthening within individuals. We found some evidence for selective disappearance of individuals with shorter telomeres through life. Early-life TL positively predicted later-life TL, but the within-individual repeatability in TL was low (9.2%). Using genetic pedigrees, we found a moderate heritability of ∆TL (h2 = 0.21), which was higher than the heritabilities of early-life TL (h2 = 0.14) and later-life TL measurements (h2 = 0.15). Cohort effects explained considerable proportions of variation in early-life TL (60%), later-life TL (53%), and ∆TL (37%), which suggests persistent impacts of the early-life environment on lifelong telomere dynamics. Individual changes in TL were independent of early-life TL. Finally, there was weak evidence for population differences in ∆TL that may be linked to ecological differences in habitat types. Combined, our results show that individual telomere biology is highly dynamic and influenced by both genetic and environmental variation in natural conditions.

Spermidine dietary supplementation and polyamines level in reference to survival and lifespan of honey bees.

Honey bee health has been an important and ongoing topic in recent years. Honey bee is also an important model organism for aging studies. Polyamines, putrescine, spermidine and spermine, are ubiquitous polycations, involved in a wide range of cellular processes such as cell growth, gene regulation, immunity, and regulation of lifespan. Spermidine, named longevity elixir, has been most analysed in the context of aging. One of the several proposed mechanisms behind spermidine actions is antioxidative activity. In present study we showed that dietary spermidine supplementation: (a) improved survival, (b) increased the average lifespan, (c) influenced the content of endogenous polyamines by increasing the level of putrescine and spermidine and decreasing the level of spermine, (d) reduced oxidative stress (MDA level), (e) increased the antioxidant capacity of the organism (FRAP), (f) increased relative gene expression of five genes involved in polyamine metabolism, and (g) upregulated vitellogenin gene in honey bees. To our knowledge, this is the first study on honey bee polyamine levels in reference to their longevity. These results provide important information on possible strategies for improving honey bee health by introducing spermidine into their diet. Here, we offer spermidine concentrations that could be considered for that purpose.

Evaluation of diverse soybean genotypes for seed longevity and its association with seed coat colour.

Sixty genotypes with different seed coat colour and seed sizes were evaluated for seed longevity under both natural and accelerated ageing over seasons. The genotypes were grown during rabi, 2018, and summer, 2021, and freshly harvested seeds were used. For natural ageing, seeds were stored in a cloth bag in ambient condition and were removed at bimonthly intervals till 20 months. Accelerated ageing was carried out as per International Seed Testing Association (ISTA) guidelines. The germination percentage after natural and accelerated ageing over two seasons was determined. The correlation between two seasons of accelerated ageing and month-wise natural ageing was highly significant. The principal component analysis (PCA) using seed longevity grouped the majority of black genotypes into a separate cluster. Higher seed longevity was associated with black seed coat colour and small seed size. Microsatellite marker-based clustering also produced a separate cluster for majority of black genotypes and grouped the genotypes into a large number of clusters suggesting high diversity in the plant material. Two black seed coat colour genotypes, ACC No.369 and ACC No.39 consistently showed higher longevity under natural and both the years of accelerated ageing and serve as a source of alleles for higher seed longevity in soybean.

A proteasomal ß5 subunit of Haemonchus contortus with a role in the growth, development and life span.

BACKGROUND: The proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic diseases, but few studies of proteasomes have been done on parasitic nematodes. METHODS: A proteasomal ß5 subunit encoding gene (named Hc-pbs-5) and its inferred product (Hc-PBS-5) in Haemonchus contortus were identified and characterized in this study. Then, the transcriptional profiles and anatomical expression were studied using an integrated molecular approach. Finally, a specific proteasome inhibitor bortezomib (BTZ), together with RNA interference (RNAi), was employed to assess the function of Hc-PBS-5. RESULTS: Bioinformatic analysis revealed that the coding sequence of Hc-pbs-5 was 855 bp long and encoded 284 amino acids (aa). The predicted protein (Hc-PBS-5) had core conservative sequences (65-250 aa) belonging to N-terminal nucleophile (Ntn) family of hydrolases. Real-time PCR results revealed that Hc-pbs-5 was continuously transcribed in eight developmental stages with higher levels at the infective third-stage larvae (L3s) and adult males of H. contortus. Immunohistochemical results revealed that Hc-PBS-5 was expressed in intestine, outer cuticle, muscle cells under the outer cuticle, cervical glands and seminal vesicles of male adults and also in intestine, outer cuticle, cervical glands, uterine wall, eggs and ovaries of female adults of H. contortus. BTZ could reduce proportions of egg hatching, and the fourth-stage larvae (L4s) developed from the exsheathed L3s (xL3s) of H. contortus. In addition, silencing Hc-pbs-5 by soaking the specific double-stranded RNA (dsRNA) could decrease the transcription of Hc-pbs-5 and result in fewer xL3s developing to L4s in vitro. CONCLUSIONS: These results indicate that proteasomal ß5 subunit plays an important role in the growth, development and life span of H. contortus.

The Other Side of the ACEs Pyramid: A Healing Framework for Indigenous Communities.

For over two decades, extensive research has demonstrated significant associations between adverse childhood events (ACEs) and a wide range of negative health, mental health, and social outcomes. For Indigenous communities globally, colonization and historical trauma are commonly associated with ACEs, and these effects reverberate through generations. While the ACEs conceptual framework expanded pyramid is a useful model and a visual aid for understanding the historical and present-day dimensions of ACEs in Indigenous communities, a healing conceptual framework is needed to outline a path toward increased community well-being. In this article, we provide a holistic Indigenous Wellness Pyramid that represents the other side of the ACEs pyramid to guide pathways toward healing in Indigenous communities. In this article, the authors describe the Indigenous Wellness Pyramid according to each of the following contrasts with the ACEs pyramid: Historical Trauma-Intergenerational Healing/Indigenous Sovereignty; Social Conditions/Local Context-Thriving Economic and Safe Communities; ACEs-Positive Childhood, Family, and Community Experiences; Disrupted Neurodevelopment-Consistent Corrective Experiences/Cultural Identity Development; Adoption of Health Risk Behaviors-Cultural Values and Coping Skills; Disease Burden and Social Problems-Wellness and Balance; Early Death-Meaningful Life Longevity. We provide examples, supporting research, and implications for implementing the Indigenous Wellness Pyramid.

Polygonati Rhizoma Polysaccharide Prolongs Lifespan and Healthspan in Caenorhabditis elegans.

Polygonati Rhizoma is the dried rhizome of Polygonatum kingianum coll.et hemsl., Polygonatum sibiricum Red. or Polygonatum cyrtonema Hua, and has a long history of medication. Raw Polygonati Rhizoma (RPR) numbs the tongue and stings the throat, while prepared Polygonati Rhizoma (PPR) can remove the numbness of the tongue, and at the same time enhance its functions of invigorating the spleen, moistening the lungs and tonifying the kidneys. There are many active ingredients in Polygonati Rhizoma (PR), among which polysaccharide is one of the most important active ingredients. Therefore, we studied the effect of Polygonati Rhizoma polysaccharide (PRP) on the lifespan of Caenorhabditis elegans (C. elegans) and found that polysaccharide in PPR (PPRP) was more effective than Polysaccharide in RPR (RPRP) in prolonging the lifespan of C. elegans, reducing the accumulation of lipofuscin, and increasing the frequency of pharyngeal pumping and movement. The further mechanism study found that PRP can improve the anti-oxidative stress ability of C. elegans, reduce the accumulation of reactive oxygen species (ROS) in C. elegans, and improve the activity of antioxidant enzymes. The results of quantitative real-time PCR(q-PCR) experiments suggested that PRP may prolong the lifespan of C. elegans by down-regulating daf-2 and activating daf-16 and sod-3, and the transgenic nematode experiments were consistent with its results, so it was hypothesized that the mechanism of age delaying effect of PRP was related to daf-2, daf-16 and sod-3 of the insulin signaling pathway. In short, our research results provide a new idea for the application and development of PRP.

Promoting the well-being of rural elderly people for longevity among different birth generations: A healthy lifestyle perspective.

Background: Wellbeing may have a protective role in health maintenance. However, no specific study clarified the particular protective effect of the subjective wellbeing of rural elderly people on survival probability. Few studies have examined the effect of the lifestyle of rural elderly people on their subjective wellbeing from different perspectives. We investigated whether improving subjective wellbeing increased the probability of longevity of rural elderly people and the effects of lifestyle behaviors on the subjective wellbeing of rural elderly people in different birth generations. Materials and methods: Data were derived from the China Health and Nutrition Survey (CHNS), which is an ongoing open cohort study that adopts a multistage, random clustered sampling process. We used the data of elderly people who were aged 65 or over during 2006-2015 for analysis. The Kaplan-Meier method and log-rank test found that the survival probability of rural elderly people was significantly lower than urban elderly people. Based on a sample of rural elderly people, Cox regression and generalized estimating equations were performed as further analyses. Results: A total of 892 rural elderly people aged 65 or over were included in the sample in 2006. High subjective wellbeing was a protective factor against death. The subjective wellbeing of rural elderly people born in the 1940s/1930s/1908-1920s birth generations first decreased then increased. For rural elderly people born in the 1940s, there were significant positive effects of a preference for eating vegetables and walking/Tai Chi on subjective wellbeing. For rural elderly people born in the 1930s, preferences for eating vegetables, reading, and watching TV all had significant positive effects on subjective wellbeing. Rural elderly people born in the 1908-1920s who preferred watching TV had more subjective wellbeing. Conclusion: Improving subjective wellbeing extended the life span and reduced mortality risk in rural elderly people and may be achieved by the shaping of a healthy lifestyle, such as preferences for eating vegetables, walking/Tai Chi, and reading.

Lifespan psychosocial stressors, optimism, and hemodynamic acute stress response in a national sample.

OBJECTIVE: To understand the association between psychosocial stressors and cardiovascular health by evaluating: (a) lifespan patterns of childhood and adulthood stressors in relation to hemodynamic acute stress reactivity and recovery and (b) the role of optimism in these associations. METHOD: Participants (n = 1,092, 56% women, 21% racial/ethnic minority, Mage = 56.2) were from the Midlife in the United States Study II Biomarker Project. Lifespan profiles of psychosocial stressor exposure (low lifespan exposure, high childhood only, high adulthood only, persistent exposure) were constructed from responses to the Childhood Trauma Questionnaire and a life events inventory. Optimism was measured with the Life Orientation Test-Revised. Hemodynamic acute stress reactivity to and recovery from cognitive stressors were assessed using a standardized laboratory protocol involving continuous measurements of systolic and diastolic blood pressure (BP) and baroreflex sensitivity (BRS). RESULTS: Compared with the low lifespan exposure group, the high childhood- and persistent-exposure groups showed lower BP reactivity, and to a lesser extent, slower BP recovery. Persistent exposure was also associated with slower BRS recovery. Optimism did not modify the association between stressor exposure and any hemodynamic acute stress responses. However, in exploratory analyses, greater stressor exposure across all developmental periods was indirectly associated with reduced BP acute stress reactivity and slower recovery via lower optimism levels. CONCLUSIONS: Findings support childhood as a unique developmental period wherein high adversity exposure may exert an enduring influence on adulthood cardiovascular health by limiting individuals' capacity to cultivate psychosocial resources and altering hemodynamic responses to acute stressors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Landmark-based spatial navigation across the human lifespan.

Human spatial cognition has been mainly characterized in terms of egocentric (body-centered) and allocentric (world-centered) wayfinding bhavior. It was hypothesized that allocentric spatial coding, as a special high-level cognitive ability, develops later and deteriorates earlier than the egocentric one throughout lifetime. We challenged this hypothesis by testing the use of landmarks versus geometric cues in a cohort of 96 deeply phenotyped participants, who physically navigated an equiangular Y maze, surrounded by landmarks or an anisotropic one. The results show that an apparent allocentric deficit in children and aged navigators is caused specifically by difficulties in using landmarks for navigation while introducing a geometric polarization of space made these participants as efficient allocentric navigators as young adults. This finding suggests that allocentric behavior relies on two dissociable sensory processing systems that are differentially affected by human aging. Whereas landmark processing follows an inverted-U dependence on age, spatial geometry processing is conserved, highlighting its potential in improving navigation performance across the lifespan.

Muscle PARP1 inhibition extends lifespan through AMPKα PARylation and activation in Drosophila.

Poly(ADP-ribose) polymerase-1 (PARP1) has been reported to play an important role in longevity. Here, we showed that the knockdown of the PARP1 extended the lifespan of Drosophila, with particular emphasis on the skeletal muscle. The muscle-specific mutant Drosophila exhibited resistance to starvation and oxidative stress, as well as an increased ability to climb, with enhanced mitochondrial biogenesis and activity at an older age. Mechanistically, the inhibition of PARP1 increases the activity of AMP-activated protein kinase alpha (AMPKα) and mitochondrial turnover. PARP1 could interact with AMPKα and then regulate it via poly(ADP ribosyl)ation (PARylation) at residues E155 and E195. Double knockdown of PARP1 and AMPKα, specifically in muscle, could counteract the effects of PARP1 inhibition in Drosophila. Finally, we showed that increasing lifespan via maintaining mitochondrial network homeostasis required intact PTEN induced kinase 1 (PINK1). Taken together, these data indicate that the interplay between PARP1 and AMPKα can manipulate mitochondrial turnover, and be targeted to promote longevity.

Creativity across the lifespan: changes with age and with dementia.

BACKGROUND: It is well known that older age is associated with losses in cognitive functioning. Less is known about the extent to which creativity is changing with age or dementia. Aim of the current study was to gain more insights into psychometric aspects of creativity in younger and older people as well as people with dementia. METHOD: Our sample comprised three groups, (1) participants between age 18-30 years (n = 24), (2) participants 65 + years without cognitive impairment (n = 24), and (3) participants 65 + years with cognitive impairment / dementia (n = 23). Cognitive abilities were assessed via the Standard Progressive Matrices Test (SPM), Montreal Cognitive Assessment Test (MoCa), and Trail Making Test (TMT). Creativity was assessed via the Creative Reasoning Task (CRT), Test of Creative Thinking-Drawing Production (TCT-DP), and Alternate Uses Task (AUT). RESULTS: Compared to younger people, older people scored significantly lower in only two out of eleven creativity sub-scores (one in the CRT and one in the TCT-DP). Performance in the SPM was significantly associated with these two sub-scores and age. Cognitively impaired older people had significantly lower scores in the creativity task AUT compared to cognitively healthy older people and younger people. The associations between MoCa and AUT scores were also significant. CONCLUSION: Creativity appears relatively stable in older age, with exception of those creativity skills that are affected by abstract reasoning (SPM), which appear susceptible to aging. As our findings suggest, cognitive impairment in older age might impair only some aspects of creativity with other creativity aspects being comparable to cognitively healthy people. The age-related and the cognitive status-related effects seem to be independent. The preserved creative abilities can be used in dementia care programs.

Effects of Parental Dietary Restriction on Offspring Fitness in Drosophila melanogaster.

Dietary restriction (DR) is a well-established strategy to increase lifespan and stress resistance in many eukaryotic species. In addition, individuals fed a restricted diet typically reduce or completely shut down reproduction compared to individuals fed a full diet. Although the parental environment can lead to changes epigenetically in offspring gene expression, little is known about the role of the parental (F0) diet on the fitness of their offspring (F1). This study investigated the lifespan, stress resistance, development, body weight, fecundity, and feeding rate in offspring from parental flies exposed to a full or restricted diet. The offspring flies of the parental DR showed increases in body weight, resistance to various stressors, and lifespan, but the development and fecundity were unaffected. Interestingly, parental DR reduced the feeding rate of their offspring. This study suggests that the effect of DR can extend beyond the exposed individual to their offspring, and it should be considered in both theoretical and empirical studies of senescence.

Downregulation of Plasma Membrane Ca2+ ATPase driven by tyrosine hydroxylase-Gal4 reduces Drosophila lifespan independently of effects in neurons.

In Drosophila melanogaster, several Gal4 drivers are used to direct gene/RNAi expression to different dopaminergic neuronal clusters. We previously developed a fly model of Parkinson's disease, in which dopaminergic neurons had elevated cytosolic Ca2+ due to the expression of a Plasma Membrane Ca2+ ATPase (PMCA) RNAi under the thyroxine hydroxylase (TH)-Gal4 driver. Surprisingly, TH-Gal4>PMCARNAi flies died earlier compared to controls and showed swelling in the abdominal area. Flies expressing the PMCARNAi under other TH drivers also showed such swelling and shorter lifespan. Considering that TH-Gal4 is also expressed in the gut, we proposed to suppress the expression specifically in the nervous system, while maintaining the activation in the gut. Therefore, we expressed Gal80 under the direction of the panneuronal synaptobrevin (nSyb) promoter in the context of TH-Gal4. nSyb-Gal80; TH-Gal4>PMCARNAi flies showed the same reduction of survival as TH-Gal4>PMCARNAi flies, meaning that the phenotype of abdomen swelling and reduced survival could be due to the expression of the PMCARNAi in the gut. In perimortem stages TH-Gal4>PMCARNAi guts had alteration in the proventriculi and crops. The proventriculi appeared to lose cells and collapse on itself, and the crop increased its size several times with the appearance of cellular accumulations at its entrance. No altered expression or phenotype was observed in flies expressing PMCARNAi in the dopaminergic PAM cluster (PAM-Gal4>PMCARNAi). In this work we show the importance of checking the global expression of each promoter and the relevance of the inhibition of PMCA expression in the gut.

Sex-biased gene expression in nutrient-sensing pathways.

Differences in lifespan between males and females are found across many taxa and may be determined, at least in part, by differential responses to diet. Here we tested the hypothesis that the higher dietary sensitivity of female lifespan is mediated by higher and more dynamic expression in nutrient-sensing pathways in females. We first reanalysed existing RNA-seq data, focusing on 17 nutrient-sensing genes with reported lifespan effects. This revealed, consistent with the hypothesis, a dominant pattern of female-biased gene expression, and among sex-biased genes there tended to be a loss of female-bias after mating. We then tested directly the expression of these 17 nutrient-sensing genes in wild-type third instar larvae, once-mated 5- and 16-day-old adults. This confirmed sex-biased gene expression and showed that it was generally absent in larvae, but frequent and stable in adults. Overall, the findings suggest a proximate explanation for the sensitivity of female lifespan to dietary manipulations. We suggest that the contrasting selective pressures to which males and females are subject create differing nutritional demands and requirements, resulting in sex differences in lifespan. This underscores the potential importance of the health impacts of sex-specific dietary responses.