Female Lifespan Research Articles

High-quality dietary protein (essential amino acids matched to reproductive needs) partially breaks the lifespan and reproduction trade-off in lubber grasshoppers.

Finding interventions to break the trade-off between reproduction and lifespan can provide insight into physiological limitations of animals. Effects of dietary protein quality on the trade-off are currently unclear, but clarity could lead to better designed diets that match animal needs. Dietary amino acid blends matching yolk proteins support reproduction and extend lifespan in fruit flies. To test if this is conserved across species, we matched dietary amino acids to vitellogenin to test reproduction and lifespan in adult females of the lubber grasshopper. Specifically, we compared varying degrees of protein quality by manipulating dietary essential amino acids. We identified a high-quality protein diet (amino acids matched to vitellogenin, or reproductive needs) that increased reproduction and matched lifespan in comparison to diets that differed only in the ratios of essential amino acids (i.e., were isocaloric and isonitrogenous). All these diets had longer lifespan but lower reproductive output than fully fed controls. In a separate experiment, full reproduction was possible on the high-quality artificial diet when offered at a 78% higher protein quantity and with a larger lettuce supplement (~ 17% of ad libitum). Additionally, we observed that as dietary protein quality was decreased (i.e., diets were less matched to vitellogenin), reproduction was reduced, and lifespan was extended in the more extreme scenarios. Taken together, these results indicate that the balance of dietary essential amino acids plays an important role in the lifespan and reproduction trade-off, while more work needs to be conducted to find the optimal diet mix for this species.

Female Phalangium opilio use fellatio to compensate sexual avoidance

Sexual conflict arises from differences in reproductive interests between the sexes. We allowed the female harvestman Phalangium opilio to sequentially mate with two different males to examine female sexual receptivity in this species. Virgin females were more sexually receptive than non-virgins. Males exhibited a high interest in repeated copulations with the same female, often engaging in aggressive behaviours such as biting and reversed sexual cannibalism. Fellatio, a behaviour in which females lick the male’s penis, was observed in 44% of trials and was associated with female unwillingness to mate and shorter copulation duration. Fellatio was repeatable, suggesting that it is influenced by individual characteristics or underlying physiological factors. Female lifespan was negatively correlated with the total number of eggs produced, suggesting a trade-off between reproduction and longevity. These findings provide evidence of the appearance of fellatio, a female mating strategy that evolved as compensation of avoiding unwanted sexual intercourse.

The lifespan of corpora lutea in nonpregnant females is positively correlated with gestation length

Abstract In mammals, a temporary endocrine gland called the corpus luteum forms on the ovary shortly after ovulation and is required for the initiation and maintenance of early pregnancy. However, the corpus luteum persists even when fertilization or pregnancy does not occur, and species-specific variation in the length of this persistence remains enigmatic. Here we perform a comparative evolutionary study across 72 species and show that corpus luteum lifespan in nonpregnant females is positively correlated with gestation length. We argue that the most likely explanation for this correlation is physiological inertia. The corpus luteum begins secreting progesterone prior to implantation, and when pregnancy does not occur it takes time for females to degrade it and prepare the next reproductive cycle. Our study suggests that this physiological inertia is stronger in species with long gestation times.

Gut-to-brain regulation of Drosophila aging through neuropeptide F, insulin, and juvenile hormone

Dietary restriction (DR) slows aging in many animals, while in some cases, the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location to sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic signals in response to food. Here, we measure how Drosophila neuropeptide F (NPF) is secreted into adult circulation by EEC and find that specific EEC differentially respond to dietary sugar and yeast. Female lifespan is increased when gut NPF is genetically depleted, and this manipulation is sufficient to blunt the longevity benefit conferred by DR. Depletion of NPF receptors at insulin-producing neurons of the brain also increases female lifespan, consistent with observations where loss of gut NPF decreases neuronal insulin secretion. The longevity conferred by repressing gut NPF and brain NPF receptors is reversed by treating adults with a juvenile hormone (JH) analog. JH is produced by the adult corpora allata, and inhibition of the insulin receptor at this tissue decreases JH titer and extends lifespan in both males and females, while this longevity is restored to wild type by treating adults with a JH analog. Overall, EEC of the gut modulate Drosophila aging through interorgan communication mediated by a gut-brain-corpora allata axis, and insulin produced in the brain impacts lifespan through its control of JH titer. These data suggest that we consider how human incretins and their analogs, which are used to treat obesity and diabetes, may impact aging.

Effects of High-Temperature Stress on Biological Characteristics of Coccophagus japonicus Compere.

The parasitoid, Coccophagus japonicus Compere (Hymenoptera: Aphelinidae) is a dominant natural enemy of Parasaissetia nigra Nietner (Hemiptera: Coccidae), an important pest of rubber trees. Much of Chinese rubber is cultivated in hotter regions such as Yunnan and Hainan, exposing applied parasitoids to non-optimal temperatures. Therefore, C. japonicus must adapt to avoid temperature-related impacts on survival and population expansion. In this study, we monitored the survival rate, developmental duration, parasitism rate, and fecundity of C. japonicus during short-term exposures to 36 °C, 38 °C, and 40 °C for 2, 4, and 6 h, as well as continuous exposures to 32 °C and 34 °C for 3 days. The results show that short-term exposure to high-temperature stress leads to decreased survival rate of C. japonicus larvae and pupae, with survival rates declining as temperature and duration increase. High-temperature stress also delayed insect development, reduced mature egg production, shortened the body length of newly emerged females, and decreased female lifespans. Moreover, continuous high-temperature stress was found to significantly impact the development and reproduction of C. japonicus. Compared with the CK (27 °C), 3 d of continuous exposure to 34 °C prolonged developmental duration, shortened the body length and lifespan of newly emerged females, reduced survival rate and single female fecundity, and significantly decreased offspring numbers and parasitism rates. Temperatures of 36 °C, 38 °C, and 40 °C decreased the mortality time of adult females to 28.78, 16.04, and 7.91 h, respectively. Adverse temperatures also affected the insects' functional response, with 8 h of stress at 36 °C, 38 °C, and 40 °C causing the control efficiency of C. japonicus on P. nigra. This level of stress in the parasitoids was found to reduce the immediate attack rate and search effect, prolong processing time, and attenuate interference between small prey. Parasitoid efficiency was lowest following exposure to 40 °C. In this study, we determined the range of high temperatures that C. japonicus populations can tolerate under short- or long-term stress, providing guidance for future field applications.

Association of coexposure to perfluoroalkyl and polyfluoroalkyl compounds and heavy metals with pregnancy loss and reproductive lifespan: The mediating role of cholesterol

Previous studies have demonstrated the toxic effects of per- and polyfluoroalkyl substances (PFASs) and heavy metals on the reproductive system. However, the interactions and combined effects of these substances remain unexplored. This study utilizes data from the National Health and Nutrition Examination Survey to investigate the associations between coexposure to four types of PFASs, lead (Pb), mercury (Hg) and self-reported pregnancy loss and reproductive lifespan in females. Genes associated with these substances and abortion were identified via the Comparative Toxicogenomics Database. The results revealed that Ln-PFOA (IRR=1.88, 95 % CI=1.42–2.50, Ln--: log transformed), Ln-PFOS (IRR=1.58, 95 % CI=1.12–2.22), Ln-PFHxS (IRR=1.99, 95 % CI=1.57–2.52), and Ln-Hg (IRR=1.92, 95 % CI=1.41–2.43) were positively associated with the risk of pregnancy loss. Ln-PFOA (β=1.27, 95 % CI=0.28–2.27), Ln-PFOS (β=1.01, 95 % CI=0.39–1.63), Ln-PFHxS (β=0.71, 95 % CI=0.12–1.63), Ln-PFNA (β=1.15, 95 % CI=0.23–2.08), Ln-Pb (β=3.87, 95 % CI=2.58–5.15), and Ln-Hg (β=1.01, 95 % CI=0.39–1.64) exposures were positively associated with reproductive lifespan. The mixed and overall effects of coexposure to PFASs and heavy metals were positively correlated with the risk of pregnancy loss and reproductive lifespan. Cholesterol partially mediated the association with the risk of pregnancy loss, whereas delay in menopause fully mediated the association with reproductive lifespan. Significant additive interactions were observed between PFOA and Pb and between PFOS, PFHxS, PFNA and Hg at high levels of coexposure. Thirty-nine overlapping genes associated with abortion were identified for these substances, and further analyses revealed that these genes significantly interact and may contribute to abortion through oxidative stress.

8303 Analysis of Over 2.2 Million Anti-Mullerian Hormone Patient Results Across Lifespan From Birth to Over 80 Years Using a Lab Developed Chemiluminescent Immunoassay

Abstract Disclosure: C. Cheng: None. D. Alfego: None. K.Y. Chun: None. Introduction: Anti-Mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of the ovarian follicle in females and by Sertoli cells of the testes in males. AMH is best known to correlate with ovarian reserve in females. As such, AMH is among the most frequently ordered tests in reproductive age females. The clinical utility of AMH beyond ovarian reserve assessment, especially in males, pediatric and postmenopausal populations, is less commonly examined. As a national reference laboratory that serves approximately 50% of providers across the country, our large database provides an opportunity to examine the clinical utility of AMH testing in other areas of health besides fertility. Objective: To examine AMH test utilization across lifespan of males and females in the US. Methods: Retrospective AMH tests performed at Labcorp® endocrine specialty lab from year 2012 to 2023 of 2,229,845 female patients and 10,362 male patients have been analyzed. Patients with unspecified sex were excluded. Serum AMH levels from birth to 80 plus years for males vs females were compared. For clinical utility assessments, female results are separated into four age groups: pediatric (age 0-17), adult (age 18-39), perimenopausal (age 40-59), and postmenopausal (age >60), and males into pediatric (age 0-17), adult (age 18-59), and older adult (age >60). ICD-10 codes associated with testing order were reviewed for each subgroup based on age and sex Results: In postmenopausal females, AMH is most frequently ordered for evaluation of ovarian cancer, whereas menstrual disorders and PCOS make up the most frequent clinical entities associated with AMH orders in females <18 years. Fertility testing is the most common ICD-10 associated with AMH orders, particularly in reproductive age and perimenopausal females. The most common ICD-10s associated with AMH in pediatric males include delayed puberty, hypoplasia of penis, and childhood short stature. In the adult and older adult male groups, AMH is surprisingly found to also most commonly associate with fertility testing and hypogonadism, although the clinical significance of post pubertal AMH is less defined. Conclusion: AMH testing has most often been used for female fertility testing, but our data show that significant fraction (10-20%) of AMH testing is used to evaluate and manage other suspected endocrine disorders and malignancies including intersex conditions at birth, pubertal development disorder, polycystic ovarian syndrome, male gonadal disfunction at all ages and granulosa cell tumors. Analysis of our large database underscores a need for clinical study to better define AMH levels that are relevant for non-fertility-related conditions. Presentation: 6/2/2024

Reproductive outcomes after antenatal corticosteroids: Secondary analysis of 50-year follow-up of the Auckland steroid randomized trial.

Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long-term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data. This is a secondary cohort analysis of the 50-year follow-up of the Auckland Steroid Trial (1969-1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo-controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation). Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo-exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03-0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring-related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term. Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.

A-074 A Laboratory Developed Serum Anti-Mullerian Hormone Electrochemiluminescent Immunoassay: Performance and Retrospective Analysis of Over 2.2 Million Tests in Females and Males Across Lifespan

Abstract Background The quantification of serum Anti-Mullerian hormone (AMH), a glycoprotein dimer produced by granulosa cells of the ovarian follicle in females and by Sertoli cells of the testes in males, has clinical utility across lifespan in both females and males. AMH is most frequently ordered to assess fertility in females of reproductive age, where it correlates with ovarian reserve. The clinical applications of serum AMH beyond ovarian reserve assessment, especially in males, pediatric, and postmenopausal populations, include the investigation of peri-menopause transition, delayed or precocious onset of puberty, differential diagnosis of disorders of sexual development, the evaluation of male gonadal function, and as an ovarian tumor marker. The objective was to establish and validate a highly sensitive assay to quantify AMH and to use our database of more than 2 million tests to understand the clinical utility of measuring AMH across sex and lifespan. Methods A validated two-step electrochemiluminescence assay was used for the quantification of serum AMH. The analytical performance of the assay was assessed, including accuracy, precision, and dilutional linearity. ICD-10 codes ordered between 2012 and 2023 were retrospectively analyzed for each subgroup based on age and sex to determine test usage. The analysis includes results from 2,229,845 female and 10,362 male patients across lifespan. Results The AMH analytical measurement range (AMR) was determined to be 0.015 - 15.0 ng/mL with a maximum reportable concentration of 960 ng/mL when run on dilution. Both inter- and intra-assay standard accuracy and precision were ≤ ±15.4% bias and ≤ 11.0% CV for all levels. Inter- and intra-assay sample precision was ≤ 9.6% CV across the AMR. Samples diluted linearly and recovered within 80 - 120% of the expected values when diluted up to 64X. Analytical interference caused by icterus, lipemia, or hemolysis was not observed. The most common ICD-10 associated with AMH orders was for fertility testing in females of reproductive age. AMH was also ordered in females for evaluation of ovarian cancer, menstrual disorders, and PCOS. In males, common ICD-10 codes associated with AMH include delayed puberty, hypoplasia of the penis, fertility testing, hypogonadism, and childhood short stature. Conclusions This study demonstrates a highly sensitive assay for the quantification of serum AMH with clinical utility across sex and lifespan. Using retrospective data, we determined that in addition to being used primarily in fertility testing, AMH is also commonly used to evaluate and manage other endocrine disorders and malignancies, including disorders of sexual development, disorders of puberty, PCOS, male gonadal dysfunction, and granulosa cell tumors. This assay can aid in defining the clinically relevant age and sex-specific levels of AHM in non-fertility-related conditions.

Female-specific mechanisms of meiotic initiation and progression in mammalian oocyte development.

Meiosis is regulated in sexually dimorphic manners in mammals. In females, the commitment to and entry into meiosis are coordinated with the developmental program of oocytes. Female germ cells initiate meiosis within a short time window during the fetal period and then undergo meiotic arrest until puberty. However, the genetic mechanisms underlying the orchestration of oocyte development and meiosis to maximize the reproductive lifespan of mammalian females remain largely elusive. While meiotic initiation is regulated by a sexually common mechanism, where meiosis initiator and Stimulated by Retinoic Acid Gene 8 (STRA8) activate the meiotic genes, the female-specific mode of meiotic initiation is mediated by the interaction between retinoblastoma (RB) and STRA8. This review highlights the female-specific mechanisms of meiotic initiation and meiotic prophase progression in the context of oocyte development. Furthermore, the downstream pathway of the RB-STRA8 interaction that may regulate meiotic arrest will be discussed in the context of oocyte development, highlighting a potential genetic link between the female-specific mode of meiotic entry and meiotic arrest.

Early life food intake modulates effects of diet restriction on lifespan and fecundity in later life in a predatory mite (Acari: Phytoseiidae)

Abstract The nutritional status of an individual can significantly influence its life history traits, including development, growth, reproduction, and survival. In the predatory mite Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae), the plasticity of life history traits, such as developmental time and size at maturity, is influenced by the quality and quantity of food. This study aimed to investigate the effects of dietary restriction at different life stages (i.e., juvenile, early adulthood, and later adulthood) on the lifespan and fecundity of P. persimilis. We found that reduced dietary intake during early adulthood resulted in a shorter lifespan for both male and female P. persimilis. Furthermore, this study demonstrated a sex-specific response to dietary restriction: it extended the lifespan of males but reduced that of females during later adulthood. Diet restriction during the postovipositional period of females showed the most variable life history trait response. Our results showed that the impact of diet restriction at different life stages can have combined influences on the postovipositional duration of P. persimilis, where the individuals receiving diet restriction during immature development and early adulthood had a greater reduction in ovipositional duration as those experiencing diet restriction during late adulthood. In addition, we observed a positive correlation between the lifespan and fecundity of females, with higher prey availability increasing both. The insights obtained from our research contribute to a better understanding of the aging process and dietary requirements of P. persimilis, which can facilitate the development of more effective biological control strategies using this predator for spider mites in agriculture.

Associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan: A cross-sectional study in U.S. women

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999–2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396–0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (β: 0.667, 95 % CI: 0.120–1.213) and reproductive lifespan (β: 0.686, 95 % CI: 0.092–1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival.

The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGO) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the ovarian reserve. Conditional loss of CHD4 in perinatal mouse oocytes results in acute death of NGOs and depletion of the ovarian reserve. CHD4 establishes closed chromatin at regulatory elements of pro-apoptotic genes to prevent cell death and at specific genes required for meiotic prophase I to facilitate the transition from meiotic prophase I oocytes to meiotic arrested NGOs. In addition, CHD4 establishes closed chromatin at the regulatory elements of pro-apoptotic genes in male germ cells, allowing male germ cell survival. These results demonstrate a role for CHD4 in defining a chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of both female and male germ cells.

Biocontrol performance and mass production potential of the larval endoparasitoid Campoletis chlorideae Uchida (Hymenoptera: Ichneumonidae) against the fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae)

BackgroundThe fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is an aggressive pest species that causes severe economic losses in outbreak regions. Use of FAW natural enemies, particularly native parasitoids, has been suggested as a promising control strategy. Campoletis chlorideae Uchida (Hymenoptera: Ichneumonidae) is a solitary ichneumonid larval endoparasitoid with a broad host range that includes S. frugiperda. However, its parasitism rate, developmental stages, and population dynamics during parasitization of S. frugiperda remain unclear. A field survey was conducted to determine the emergence rate and sex ratio of C. chlorideae, evaluated the biological control performance, and investigated the production potential of it on the individually reared and group-reared S. frugiperda through age-stage, two-sex life tables, respectively.ResultsThe results showed that C. chlorideae parasitizing individually reared FAW resulted for the parasitoid in a lifetime total fecundity (F) of 301.5 ± 16.4 eggs/female, a net reproduction rate (R0) of 62.03 ± 9.07 adult females/female, an overall life span of females of 28.3 ± 0.52 days, and an intrinsic rate of increase (r) of 0.1946 ± 0.0076 day−1. In contrast, the parameters of F, R0, overall life span of females, and r were 87.71 ± 6.32 pupae/female, 6.02 ± 1.61 adult females/female, 25.21 ± 0.79 days, and 0.0918 ± 0.0148 day−1 in group-reared S. frugiperda.ConclusionsThis study suggests that C. chlorideae has a promising biological control potential against S. frugiperda. Future research should focus on developing methods to increase the production of C. chlorideae.

Spatiotemporal single-cell RNA sequencing reveals the role of steroid hormone pathway during chicken primordial follicle formation

The size of the initial primordial follicle pool in the ovary depends on primordial follicle formation, which determines the female reproductive lifespan. However, the molecular regulation of primordial follicle formation in chickens remains unclear. In this study, the left ovaries of chickens were collected at 2 d posthatch (dph), 5.5 dph, and 10.5 dph to examine the formation of primordial follicles. Single-cell mRNA sequencing (scRNA-seq) and spatial transcriptomic analysis were performed to explore the ovarian microenvironment and identify regulatory pathways involved in the formation of primordial follicles in chickens. Histomorphological analysis of chicken ovary tissues revealed the presence of germ cell cysts at 1 dph, which began to disintegrate at 2 dph. Primordial follicles appeared at 5.5 dph and continued to develop into larger-diameter follicles. scRNA-seq and spatial transcriptomic analysis revealed 24 cellular clusters involved in chicken primordial follicle formation. The metabolic pathway of steroid hormone synthesis was found in pregranulosa and pretheca cells. Histological analysis showed that chicken ovaries did not form primordial follicles after the inhibition of the steroid hormone synthesis pathway by simvastatin or tamoxifen. In addition, mRNA transcriptomic and bioinformatics analyses revealed that GREB1 was a downstream gene of the steroid hormone synthesis pathway during the formation of chicken primordial follicles. This study provides a valuable foundation for investigating primordial follicle formation in avian species and optimizing their reproductive performance.

Conditional Inhibition of Eip75B Eliminates the Effects of Mating and Mifepristone on Lifespan in Female Drosophila.

Mating in female Drosophila melanogaster causes midgut hypertrophy and reduced lifespan, and these effects are blocked by the drug mifepristone. Eip75B is a transcription factor previously reported to have pleiotropic effects on Drosophila lifespan. Because Eip75B null mutations are lethal, conditional systems and/or partial knock-down are needed to study Eip75B effects in adults. Previous studies showed that Eip75B is required for adult midgut cell proliferation in response to mating. To test the possible role of Eip75B in mediating the lifespan effects of mating and mifepristone, a tripartite FLP-recombinase-based conditional system was employed that provides controls for genetic background. Expression of a Hsp70-FLP transgene was induced in third instar larvae by a brief heat pulse. The FLP recombinase catalyzed the recombination and activation of an Actin5C-GAL4 transgene. The GAL4 transcription factor in turn activated expression of a UAS-Eip75B-RNAi transgene. Inhibition of Eip75B activity was confirmed by loss of midgut hypertrophy upon mating, and the lifespan effects of both mating and mifepristone were eliminated. In addition, the negative effects of mifepristone on egg production were eliminated. The data indicate that Eip75B mediates the effects of mating and mifepristone on female midgut hypertrophy, egg production, and lifespan.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

A novel method for quantifying affective sensitivity to endogenous ovarian hormones

Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related mood disorders, perinatal mood disorders, and perimenopausal depression. Developing a method to accurately quantify sensitivity to endogenous hormone fluctuations may therefore facilitate the prediction and prevention of these mental health conditions. Here, we propose one such method applying a synchrony analysis to compute time-lagged cross-correlations between repeated assessments of endogenous hormone levels and self-reported affect. We apply this method to a dataset containing frequent repeated assessments of affective symptoms and the urinary metabolites of estradiol (E2) and progesterone (P4) in 94 perimenopausal females. These preliminary findings suggest that, with further refinement and validation, the proposed method holds promise as a diagnostic tool to be used in clinical practice and to advance research investigating the etiology of reproductive mood disorders.

Correction to: Do Female Life Span and Fecundity of Small Ermine Moth Increase with Multiple Mating and Adult Nutrition?

Correction to: Do Female Life Span and Fecundity of Small Ermine Moth Increase with Multiple Mating and Adult Nutrition?

Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin.

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.