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Results for “reproductive senescence”

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17 recordsLinked to original sources
PubMed1978

Hypothalamic-pituitary-ovarian interactions during reproductive senescence in the rat.

The neuroendocrine status of Long-Evans female rats was evaluated at several key stages of reproductive senescence. Young (4-8 mo), middle-aged (10-14 mo) and old (24-30 mo) animals were studied according to reproductive state. The reproductive states studied were (1) regularly cycling, (2) constant estrus and (3) pseudopregnant, as determined by vaginal smear cytology. Neuroendocrine parameters at the levels of the hypothalamus, pituitary and steroid-producing organs were compared between each group. DA3, E and NE concentrations in the median eminence of the hypothalamus were determined by a highly sensitive radioenzymatic assay. LRF content in the median eminence was measured by radioimmunoassay. Circulating levels of LH, FSH, PRL and six steroids were determined. Changes in hormone and neurotransmitter concentrations were deomonstrated in association with the various stages of reproductive senescence and with age advancement. These changes involved the hypothalamic, pitiutary and steroid systems. NE content in the median eminence, FSH in serum and circulating androstenedione were all significantly increased in middle-aged, cyclic rats prior to the onset of senescent anovulation. DA concentration in 24 mo. old constant estrous rats (30.7 +/- 7.7 pg/microgram, N = 6) and in 30 mo. old pseudopregnant rats (27.5 +/- 7.1 pg/microgram, N = 6) was significantly reduced compared to young (6 mo. old), cyclic controls on proestrous (55.0 +/- 4.7 pg/microgram, N = 12). This DA reduction was associated with a 3-fold increase in circulating prolactin. The results are discussed in terms of a regulatory cascade model of female reproductive senescence (Finch, 1976).

Aging↗
PubMed2026

Mitochondrial Haplotype Shapes the Trajectory of Ovarian Aging in Genetically Heterogeneous Rats.

Ovarian aging leads to permanent reproductive senescence and systemic hormonal changes that predispose women to age-associated comorbidities. Despite these observations, the intrinsic mechanisms driving age-related ovarian decline are poorly defined. Mitochondrial DNA (mtDNA) mutations and instability are strongly associated with aging; however, it remains unknown if naturally occurring mitochondrial genetic variation influences the trajectory of ovarian aging. To address this, we compared two genetically heterogeneous rat cohorts (OKC-HETB and OKC-HETW) that differ in mitochondrial haplotype on a randomized but equivalently distributed nuclear background. The OKC-HETW haplotype was associated with accelerated loss of primordial follicles and pathological remodeling marked by fibrosis, macrophage infiltration, and multinucleated giant cells. These tissue-level pathologies were paralleled by mitochondrial dysfunction, characterized by decreased respiratory complex activity, ATP production, and mtDNA copy number. Mechanistically, we identified a haplotype-specific defect in mitochondrial genome maintenance. Although TFAM expression was normal, and total TFAM protein was elevated, OKC-HETW ovaries showed reduced mitochondrial TFAM abundance, TFAM-mtDNA binding, and TOMM20, suggesting that impaired TOMM20-mediated import is associated with compromised mitochondrial genomic stability. Longitudinal transcriptomic and proteomic analyses further indicate that mitochondrial haplotype influences the rate of ovarian aging, with OKC-HETW ovaries showing accelerated activation of inflammatory and fibrotic pathways alongside suppressed proteostasis and mitochondrial function. These defects corresponded to impairments in ovulation and a trend toward worsening oocyte quality. Collectively, our findings identify mitochondrial haplotype as a heritable modifier of ovarian aging rate that acts in concert with the nuclear genome, and a putative target for preserving ovarian function and female healthspan.

Animals↗
PubMedDate not supplied

[Physiological age of the fleas and the analysis of age structure of natural population of Xenopsylla gerbilli Wagn].

A new six-graded scale is suggested instead of five-graded one proposed earlier (Kunitskaya, 1960). Analysis of the reproduction and age composition of the natural population of X. gerbilli with a use of the suggested scale enabled the authors to find out regularities in the reproduction, senescence and change of generations of these insects in South Pribalkhashke. It was established that one complete, one incomplete and possibly third partial generation develop in this region for a year.

Aging↗
PubMed1977

Laboratory maintenance, breeding, rearing, and biomedical research potential of the Yucatan octopus (Octopus maya).

Eggs of the Yucatan octopus, Octopus maya, were collected at Campeche, Mexico, transported to Hawaii, and incubated in glass funnels. Benthic juveniles hatched from the large (17-mm) eggs and were reared on a variety of live and frozen foods. As many as 200 animals were reared for the first month in a 20-liter aquarium. No disease or parasite problems were encountered and nearly all well-fed juveniles survived to sexual maturity. The species was reared through four generations in the laboratory. Animals weighed 0.1 g at hatching and within 8.5 months attained an average weight of 3231 g. Mating was promiscuous and sperm were stored in the oviducts until spawning. Spawning occurred at 8-9 months of age. Up to 5,000 eggs were laid by large females and nearly 100% of fertilized eggs developed to hatching. Females brooded eggs during the 45-day period of development but artificial was as successful as natural incubation by the mother. Pos-reproductive senescent decline of both males and females was rapid and average life span was 300 days from hatching. Areas of biomedical research in which O maya could be a useful model were suggested and included neurobiology, comparative psychology, ontogeny of behavior, immunology, endocrinology, and studies of aging.

Animal Feed↗
PubMed2026

Parental senescence effects in a short-lived fish.

Senescence is age-related decline that may carry over to subsequent generations. Advanced parental age can both improve or reduce offspring fitness, however. Identification of mechanisms of parental effects senescence thus proved challenging so far. We investigated the effects of old parental age on offspring performance in a laboratory short-lived fish, Nothobranchius furzeri (Cyprinodontiformes). We followed age-related changes in parents and then focused on the effect of parental age on key offspring life-history traits (embryonic survival, hatching rate and juvenile growth). We employed telomere length as a senescence marker and a potential route for transmitting senescence effects from parents to the offspring. As parents aged, their body condition, reproductive output, and telomere length declined. Offspring of older parents showed lower survival and hatching rate. In contrast, old parental age did not compromise juvenile growth and telomere length of the successfully hatched offspring. This, among other things, resulted in decoupling of parent-offspring telomere length. Our study highlights the sensitivity of the early life-stages to old parental age in contrast to offspring post-hatching performance.

Nothobranchius↗
PubMed2026

Sex differences in social dominance emerge late in life in a gregarious bird.

Social dominance shapes group structure and the collective behaviour of gregarious animals. Senescence, the progressive physiological deterioration associated with ageing, may influence behaviour, including social dominance, while reproductive roles may lead to different onset times or rates of senescence between the sexes. However, how ageing shapes sex differences in sociality remains poorly understood, largely due to the scarcity of long-term studies comparing male and female social behaviour. To address this gap of knowledge, we monitored dominance hierarchies during foraging in an ageing, semi-natural population of adult common waxbills (Estrilda astrild). Our study lasted 5 years, which is more than most adult waxbills would live in the wild, to facilitate detecting effects of senescence. At the onset of the study, sex differences in dominance were negligible but became pronounced with ageing during breeding seasons. In contrast, sex differences remained weak during non-breeding seasons. Females showed stronger longitudinal and seasonal changes in dominance than males, whose dominance patterns remained more consistent across breeding and non-breeding periods. Nonetheless, social dominance also increased, on average, as the number of years until death decreased. Although sex differences in animal sociality are often thought of as largely fixed, our findings reveal a dynamic pattern in which sex differences in dominance emerge with ageing and are context-dependent, varying across breeding seasons. Overall, our results suggest that senescence and seasonal context shape sociality later in life.

behavioural ageing↗
PubMed1977

Measures of fitness and demographic stability.

The concepts of entropy and reproductive potential of a genotype were introduced in a previous paper [Demetrius, L. (1974) Proc. Natl. Acad. Sci. USA 71, 4645-4647] and an analoge of the fundamental theorem of natural selection was derived. This paper relates to entropy of a population with the rate of convergence of the population to the stable age distribution. I show that (i) at maximal entropy, no oscillatory components exist and the birth sequence is unaffected by perturbations in the stable age distribution; and (ii) at zero entropy, oscillatory components occur and increase as rapidly as the real exponential component in the birth sequence. These results have implications towards (i) the relation between population fitness and adaptedness, (ii) modes of selection and the evolution of reproductive strategies, and (iii) the evolution of senescence.

Aging↗
PubMed1979

Altered neuroendocrine status of middle-aged rats prior to the onset of senescent anovulation.

The incidence of senescent anovulation (constant estrus) in female rats increases sharply in the age interval 10--14 months. We have compared the neuroendocrine status of 12-month-old rats, which were still cycling, with that of 6-month-old rats in the reproductive prime. Norepinephrine content in the median eminence of the hypothalamus and circulating levels of FSh and androstenedione were significnatly higher in middle-aged rats (12 months old) than in young controls (6 months old). These increases were selective, in that ten other neuroendocrine parameters measured were unchanged. These results indicate that changes occur at multiple levels of the neuroendocrine system during the transitional phase prior to the onset of senescent anovulation.

Age Factors↗
PubMed1978

Bidder's hypothesis revisited. Solution to some key problems associated with general molecular theory of ageing.

In this paper I consider three major difficulties associated with the general molecular theory of ageing, namely: (1) How can molecular damage accumulate in the face of the constellation of repair mechanisms that is found in cells? (2) How can the obvious programmatic nature of ageing be reconciled with underlying stochastic processes? (3) How do some organisms avoid ageing? As a solution to points 1 and 2, I propose that the repair mechanisms themselves deteriorate in a programmed fashion with age. However, I argue that this programming is unlikely to be a result of direct selection for life-shortening but, rather, is more likely to be a result of an indirect selection for other characters. This idea is very similar to the theory of senescence first formulated by Bidder. The solution to point 3 is that the repair mechanisms in systems which avoid ageing, in particular cellular and molecular turnover, are not impaired with age. The rejuvenating capacities of sexual and asexual reproduction are also discussed.

Aging↗
PubMed2026

Repair and regeneration across the lifespan: an ontogenetic perspective.

The capacity for tissue repair and regeneration undergoes a profound and progressive decline across the human lifespan, representing a fundamental driver of aging and chronic disease. This review establishes a comprehensive ontogenetic framework by mapping the continuous biological transition from the flawless, scarless regenerative plasticity of embryonic development to the irreversible fibrotic scarring and organ failure characteristic of senescence. We synthesize the hierarchical collapse of reparative networks across multiple biological scales. Importantly, this ontogenetic decline should not be interpreted as a purely degenerative trajectory but rather as a dynamic systems-level reprogramming in which evolutionary trade-offs prioritize tumor suppression, immune surveillance, and reproductive fitness over long-term regenerative fidelity. Recognizing this adaptive reallocation of biological resources reframes aging not simply as failure but as a predictable recalibration of repair hierarchies. At the molecular and cellular levels, the accumulation of genomic instability, unresolvable DNA damage, and mitochondrial dysfunction gradually overwhelms intracellular quality-control mechanisms. Concurrently, epigenetic drift and chronic, low-grade systemic inflammation ("inflammaging") dismantle the stem cell niche, driving adult stem cell exhaustion and shifting wound healing away from functional tissue replacement toward maladaptive fibrosis. Furthermore, we examine divergent, organ-specific repair trajectories. By contrasting the severe regenerative restrictions of the adult central nervous system and myocardium with the persistent, yet exhaustible, resilience of the liver, we elucidate the unique intrinsic and microenvironmental barriers that impede structural and functional recovery. Finally, we evaluate the clinical paradigm shift from passive management of age-related degeneration to active restoration of tissue integrity. By integrating systemic geroscience-which addresses the global hallmarks of aging-with targeted bioengineering and in vivo epigenetic modulation, contemporary regenerative medicine seeks to recreate permissive, youthful microenvironments. Ultimately, mastering these ontogenetic principles holds unprecedented potential to reactivate endogenous repair pathways, mitigate multi-organ collapse, and significantly extend human functional healthspan.

DNA repair↗
PubMed1977

The spermatozoan genome and fertility.

The strategy for effective reproduction by eliminating genetically unbalanced gametes during spermatogenesis and transport varies in degree of success within as well as among species, but in no animal has it been reported to be completely effective. In the human subject, for example, it is estimated that one in every 50 ejaculated spermatozoa is genetically abnormal. The causal basis of these anomalies is poorly understood. Meiotic accidents, environmental mutagens, and gamete senescence in utero are all implicated. However, many of these abnormal cells are fertile. This fact plus the weight of the evidence reviewed suggest that fertility differences among males which cannot be ascribed to measurable differences in semen characteristics reflect, in large part, the increased opportunity of nuclear defective gametes in the semen of some males to effect fertilization. The elimination of embryos arising from eggs fertilized by genetically defective spermatozoa through spontaneous abortions, although biologically costly, must be viewed as the final check for the elimination of genetic detritus of the species.

Abortion, Spontaneous↗
PubMed2025

Tonoplast sucrose transporter SUT4-dependent sugar partitioning modulates phenological transitions and reproductive success in poplar.

Climate uncertainty is intensifying the need for greater plasticity in carbohydrate reserve utilization to support winter survival and spring growth in woody perennials. In poplar, the single-copy SUT4, which encodes a tonoplast-localized sucrose transporter, and the SUT5/SUT6 genome duplicates, which encode plasma membrane-localized transporters, are expressed year-round, with SUT4 showing the highest expression during cool seasons. Given its role in vacuolar sucrose efflux and winter-predominant expression, SUT4 may play a key role in modulating seasonal carbohydrate dynamics. While SUT4-knockdown and knockout effects have been studied under greenhouse conditions, their impact under field conditions remains unexplored. Here, we report a field-based study comparing CRISPR knockout mutants of winter-expressed SUT4 and SUT5/SUT6 in Populus tremula × alba. We show that sut4, but not sut5/6, mutants exhibited earlier autumn leaf senescence, delayed spring bud flush, reduced stem growth, and altered sugar partitioning in winter xylem and bark relative to controls. After 2 years in the field, all genotypes flowered before leaf flush in early spring; however, sut4 mutants produced sterile ovules despite developing normal-looking catkins. Metabolic profiling revealed disrupted sucrose and raffinose dynamics in elongating sut4 catkins. This was accompanied by transcriptomic signatures of elevated stress and downregulation of proanthocyanidin biosynthesis and circadian clock genes. These findings highlight the critical role of SUT4 in coordinating sugar allocation, stress responses, and seasonal development in poplar.

Populus↗
PubMed1978

Embryo transfer for cows with reproductive problems.

Surgical embryo recovery and transfer methods were applied to 25 cows and heifers with chronic reproductive problems. In 16 of the 25 animals, abnormalities could not be detected by palpation per rectum and, at laparotomy, the probable cause of low fertility was found to be oviductal obstructions or periovarian adhesions in 6 of them. Four pregnancies were obtained from 3 of these 6 animals. A definitive diagnosis was not obtained through laparotomy in the other 10 animals in this group; however, an abnormal uterine environment associated with senescence may have been responsible for low fertility in the older cows. Eighteen calves were obtained by embryo transfer from 8 of these 10 donor animals. The remaining 9 heifers and cows had lesions detectable by palpation per rectum. Chronic, purulent metritis was found in 2 cows, one of which produced 7 calves by embryo transfer. The other 7 had periovarian adhesions, and 8 calves were obtained from 2 of them. The adhesions in 6 of these 7 cows were attributable to cesarean section. Laparotomy was valuable for defining the extent of the adhesions and establishing a reliable prognosis in some cases.

Animals↗
PubMed2026

Ovarian aging and systemic health: Mechanisms and emerging intervention strategies.

Ovarian aging may contribute to systemic aging via the ovarian-systemic axis. This review outlines intrinsic ovarian cellular defects such as genomic instability, epigenetic shifts, and mitochondrial and proteostasis damage, which may trigger senescence-associated secretory phenotype (SASP)-related inflammaging, fibrosis, and distal pro-aging signals. Ovarian-derived endocrine disruption, especially estrogen decline, broadly affects bodily physiology. We summarize emerging multimodal interventions, including senolytics, metabolic reprogramming, regenerative medicine, and systemic approaches, and we discuss their dual potential to preserve fertility and intercept ovarian contributions to systemic aging. Ovarian aging is possibly associated with female age-related multimorbidity. Ovary-targeted prevention may extend healthspan, as assessed by combined reproductive and systemic clinical evaluations.

Humans↗
PubMed1977

[Senescence of endocrine function with special reference to the hypothalamic-pituitary-gonadal axis in the rat (author's transl)].

In the control theories, aging is under genetic and environmental control. Endocrine function plays an important role in this control system by mediating between the environmental influence and the presumptive "aging gene". Therefore, the intrinsic aging of the hypothalamus, such as the changes in sensitivity to feedback suppression or stimulation, may lead to homostatic failure and then age-related pathology. As the subject of study we have selected the senile changes in the hypothalamic-pituitary-ovarian axis in the rat of the Wistar strain. The cessation of estrous cycle and the onset of persistent estrus or repetitive pseudopregnancy usually take place as early as at the end of the first half of life in rats. In this paper the results of the following experiments are briefly dealt with: (i) reciprocal transplantation of ovaries between young and old rats (the term "old" designates here "incapable of reproduction"), (ii) comparison of LH and FSH binding abilities in the ovarian preparations, (iii) comparison of serum and pituitary concentrations of LH, FSH and prolactin and the modifications after ovariectomy or by the administration of pharmacological drugs, and (iv) the difference between young and old rats in intensity of dopamine fluorescence in the hypothalamus. The results of these experiments seem to point to the hypothalamic-pituitary part rather than more peripheral organs (ovaries) as being primarily responsible for the outcome of the senile changes in the female rat.

Aging↗
PubMed2026

Non-syndromic premature ovarian insufficiency associated with monoallelic LIG4 mutation via haploinsufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a heterogeneous reproductive disorder, with genetic factors, particularly defects in DNA damage response pathways, increasingly implicated in its pathogenesis. DNA ligase IV (LIG4) is a key enzyme in the non-homologous end joining (NHEJ) pathway responsible for repairing DNA double-strand breaks (DSBs). However, its role in non-syndromic POI remains unclear. This study aimed to investigate the potential contribution of LIG4 variants to non-syndromic POI. RESULTS: Whole-exome sequencing identified a heterozygous frameshift variant in LIG4 (c.1271_1275del) in a three-generation Han Chinese family with non-syndromic POI, which co-segregated with affected individuals. AlphaFold-based structural modeling predicted truncation of the C-terminal XRCC4 interaction region. Functional experiments demonstrated that the mutant LIG4 protein showed reduced stability and was predominantly mislocalized to the cytoplasm of cells. In ovarian KGN cells, LIG4 depletion reduced cell viability, induced stress-associated cellular senescence, and impaired DNA damage repair capacity. In LIG4 knockout 293T cells, co-transfection of wild-type and mutant constructs revealed dose-dependent functional impairment, resulting in increased apoptosis under basal conditions and after phleomycin induced DNA damage, together with delayed repair of DSBs. Reanalysis of public single-cell RNA sequencing data further showed stage specific upregulation of LIG4 during oocyte maturation. Co-expression network analysis revealed enrichment in the Fanconi anemia pathway, phosphatidylinositol 3-kinase signaling pathway, and glycan metabolism. CONCLUSIONS: Our findings suggest that monoallelic LIG4 mutations may represent a potential genetic etiology for non-syndromic POI with sex-limited penetrance. While further validation in more physiologically relevant models is warranted, our data indicate that LIG4 haploinsufficiency may impair DSB repair and disrupt molecular pathways crucial for oocyte maturation and survival, highlighting a potential role of the NHEJ pathway in maintaining human ovarian function.

Humans↗