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Results for “Lifespan”

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At least 19 recordsLinked to original sources

PubMed2026

Di-, tri-, and tetranucleotide frequencies covary with lifespan and genome size across protostome invertebrates.

Animal lifespans span orders of magnitude, yet how genome sequence covaries with lifespan remains poorly characterized outside vertebrates. Although promoter CpG density has been linked to vertebrate longevity due to its gene-regulatory function through DNA methylation, it is unclear whether such patterns are promoter- and CpG-specific, or if they reflect broader sequence evolution. We curated maximum lifespan estimates for 466 protostome species spanning eight phyla with available genome assemblies and quantified mono-, di-, tri-, and tetranucleotide composition across whole genomes, intergenic regions, and six gene-associated regions (two upstream regions, exons, introns, and two downstream regions) defined using Benchmarking Universal Single-Copy Orthologs. Dinucleotide observed/expected ratios showed significant associations with lifespan and genome size in different ways. Lifespan-associated motifs were most pronounced in gene-associated non-coding regions, especially in introns and downstream regions, whereas genome-size effects were strongest in whole-genome and intergenic sequence. Tri- and tetranucleotide observed/expected ratios broadly recapitulated this regional organization. In contrast, GC content was not associated with lifespan across regions, indicating that the observed signals are not explained by mononucleotide composition but instead by how those nucleotides are arranged into short sequence motifs. These results suggest that lifespan and genome size show distinct but overlapping associations with regional sequence composition across invertebrate species and that lifespan-associated motif evolution extends beyond vertebrate promoter methylation architectures.

CpG density↗

PubMed1978

The effects of the epidermal and fibroblast growth factors on the replicative lifespan of cultured bovine granulosa cells.

The effects of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on the lifespan of cultured bovine granulosa cell cultures have been investigated. Granulosa cell cultures from small follicles (4-7 mm) had a lifespan of 11-12 generations, whereas the lifespan of cultures originating from large follicles did not exceed seven generations. The addition of either EGF or FGF to the medium of cultures originating from small follicles greatly increased the lifetime of the cultures, which can then exceed 60 generations. A similar, although less pronounced, effect was observed with cultures originating from large follicles. The lifespan of granulosa cell cultures depends upon the presence of FGF or EGF in the medium, as the deletion of the mitogens resulted in rapid terminal differentiation and a shortened replicative lifespan. As either FGF or EGF can prolong the replicative lifespan of granulosa cell cultures, it is suggested that limited replicative lifespan when maintained in the absence of mitogens is not so much determined by a fixed rate of mutation as it is by the culture conditions in which the cells are maintained.

Animals↗

PubMed1979

Human cells and the finite lifespan theory.

Cultures of human diploid fibroblasts are characterized by: i) finite lifespan, ii) marked heterogeneity in the growth potential of individual cells within the culture, iii) considerable variation in lifespans of parallel cultures of the same cell strain. To explain these properties, we have proposed a commitment theory of cellular aging. Cells are assumed initially to be uncommitted (potentially immortal) but, at each cell division, each daughter cell is assumed to have some fixed probability of becoming irreversibly committed to senesce and die after a specific number of cell generations. During the period between commitment and senescence, cells are assumed to multiply normally, so the uncommitted cells are diluted by committed ones and may be lost in subculturing. The theory explains features i) - iii) above and, in particular, suggests why diploid cultures have finite lifespans while transformed or permanent lines grow indefinitely. It also validly predicts the behaviour of mixed cultures of distinguishable but otherwise similar cell types, and that culture lifespan may be significantly decreased by drastic reduction of population size. The important converse prediction that culture lifespan may be extended indefinitely by growing sufficiently large cultures or by selectively isolating uncommitted cells remains to be tested.

Cell Division↗

PubMed2024

Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.

Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (ageing-associated lncRNA), which is induced in quiescent fission yeast cells. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression prolongs their lifespan, indicating that aal1 acts in trans. Overexpression of aal1 represses ribosomal-protein gene expression and inhibits cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 lncRNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 overexpression decreases the cellular ribosome content and inhibits protein translation. The aal1 lncRNA binds to the rpl1901 mRNA, encoding a ribosomal protein. The rpl1901 levels are reduced ~2-fold by aal1, which is sufficient to extend lifespan. Remarkably, the expression of the aal1 lncRNA in Drosophila boosts fly lifespan. We propose that aal1 reduces the ribosome content by decreasing Rpl1901 levels, thus attenuating the translational capacity and promoting longevity. Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.

RNA, Long Noncoding↗

PubMed2026

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2 years) and the longer-lived cold-water Argopecten purpuratus (7-10 years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56 days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30 days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56 days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae↗

PubMed1979

The effect of ginseng on lifespan and stress responses in mice.

It has been suggested that ginseng can increase long-term resistance to stress and disease and therefore affect the lifespan. We set out to investigate this idea by testing whether the continuous administration of ginseng could affect the lifespan of mice and/or their behavioural responses to stress. 270 mice of strain LACa were divided into three groups: one group which was given ginseng from 8 weeks of age, a second group which was given ginseng from 52 weeks of age and an untreated control group. The mice were generally healthy. Their weights remained stable throughout their lifespan and were not altered by ginseng. Ginseng administration did not significantly alter the lifespan. However, ginseng did cause an exaggeration of the behavioural responses to mild stress. This effect was noticeable soon after ginseng administration and subsequently was maintained.

Animals↗

PubMed1979

Similarity in the number of lifespan heartbeats among non-hibernating homeothermic animals.

An investigation was made of the available data on heart rates and maximum lifespan of a number of vertebrates from a variety of sources; only data pertinent to resting adult non-anesthesized homeothermic mammals and birds in a state of thermal neutrality were subsequently analyzed. All known hibernators were excluded because of their extreme, and largely unknown, range of heartbeat from season to season. Plots of heart rate (beats per minute) against reciprocal of lifespan in years showed surprisingly good fits (r = +0.90 for mammals and r = +0.64 for birds). Computation of the total number of heartbeats in the maximum recorded lifespans of the mammalian and avian species involved in this study showed that the mean cumulative heartbeat number for 31 mammalian species was 100 +/- 8 S.E.M. x 10(7) beats and for 23 avian species was 326 +/- 22 S.E.M. x 10(7) beats. This paper documents this analysis, which supports the concept of a close similarity in lifespan heartbeats among mammalian species and among avian species.

Animals↗

PubMed2026

Genetic interactions between PIWI subfamily genes and hobo transposons modulate Drosophila melanogaster lifespan under chronic low-intensity irradiation.

In recent decades, there has been active research into how ionizing radiation at low doses, an inevitable factor in human activity, affects aging processes and which molecular genetic mechanisms underlie this influence. This study investigates the effects of mutations in PIWI subfamily genes (piwi and aub), which regulate transposable elements, on the lifespan of Drosophila melanogaster under conditions of genome instability induced by hobo transposons and chronic low-intensity irradiation (20 cGy). It is shown that dysfunction of piwi and aub modulates the activity of hobo transposons, increasing the frequency of their excisions/transpositions and recombinogenic activity, as confirmed by phenotypic and PCR analyses. The presence of hobo transposons in the genome elevates the spontaneous level of DNA fragmentation in ovarian cells, and chronic irradiation enhances this effect, leading to increased DNA damage in somatic and germline cells of most studied strains. Despite increased genetic instability and reduced fertility in some genotypes, the combined presence of mutations and hobo transposons paradoxically increases lifespan both under control conditions and after irradiation. Analysis of the interaction between genetic factors reveals a predominantly antagonistic, and in one case synergistic, effect on lifespan, depending on the type of mutation, the structure of the hobo transposons (full-size or defective copies), sex, and irradiation conditions. These results demonstrate the complex interplay between systems controlling transpositional activity and stress-induced processes that affect key viability parameters.

Animals↗

PubMedDate not supplied

Changes in albumin uptake during the lifespan of human fibroblasts in vitro.

It has been suggested that a deterioration of cell membrane functions in cell populations with a limited lifespan in vitro could explain the loss of division potential either through changes in permeability of in cell attachment. We analyzed membrane function measuring the uptake of iodinated human serum albumin (125ISA) at different passages during the lifespan in vitro of human adult lung fibroblasts. Monolayers were incubated with 100microng/ml 125ISA. One and sixty minutes later, cultures were washed and the cell bound radioactivity was determined; these values correspond respectively to adsorption and net uptake. Our results show a significant increased uptake of albumin by aging cells. The changes in cell permeability, however, are apparent only late during the life span. Old cultures were also more susceptible to the stimulatory action of polyornithine (PLO) on protein uptake. Results obtained with PLO on young cells showed that the cell takes up more albumin when there is membrane danage leading to leakage of proteins. These findings suggest that the increased uptake of albumin and the suceptibility to PLO are signs of membrane damage in cells that have reached the end of their lifespans. In that case, an increased protein uptake would be the prelude to cell death.

Cell Membrane Permeability↗

PubMed1977

The effect of oxygen and vitamin E on the lifespan of human diploid cells in vitro.

Human diploid cells (WI-38) were serially subcultivated at partial pressures of oxygen (Po2) ranging from 5.6 mm Hg to 608 mm Hg. At a Po2 of 5.6 mm Hg, the number of doublings to phase out was less than that of control cells at a Po2 of 137 mm Hg. Cultures grown at Po2's of 24, 49, or 137 mm Hg grew at the same rate and phased out after a similar number of population doublings. Population lifespan was markedly shortened by chronic exposure to elevated Po2's, a phenomenon that was, in part, reversible. d-1-alpha-Tocopherol (10 microgram/ml or 100 microgram/ml) homogenized into the medium at each weekly subcultivation did not extend the lifespan of cells at reduced, ambient, or elevated oxygen tensions. These results indicate that neither oxygen toxicity nor free radical reactions play a significant role in limiting the lifespan of WI-38 cells grown in vitro under ambient oxygen tensions (Po2 137 mm Hg).

Cell Division↗

PubMed1978

Erythropoiesis and mean red-cell lifespan in normal subjects and in patients with the anaemia of active rheumatoid arthritis.

Recently developed ferrokinetic methods offer a tool to measure effective and ineffective erythropoiesis and mean red-cell lifespan (Ricketts et al, 1975). We have used this tool to investigate erythropoiesis in normal subjects and in patients with the anaemia of active rheumatoid arthritis. In normal subjects the results are comparable with the results published by Cavill et al (1977). In patients with the anemia of active rheumatoid arthritis there appears to be a total and an effective red-cell production as in the normal subjects. The ineffective erythropoiesis in the patients is increased and the produced red cells have a shortened mean lifespan in the circulation. The increased ineffective erythropoiesis is probably due to inadequate supply of iron to the marrow and the shortened mean red-cell lifespan to an extra-corpuscular haemolytic factor. The impaired marrow response to the anaemia of active rheumatoid arthritis has been confirmed.

Adult↗

PubMedDate not supplied

Phenomenological structuring of the adult lifespan as a function of age and sex.

The hypothesis that increasing differentiation in the phenomenological structure of the lifespan can be expected to occur during adolescence and early adulthood, stabilization during adulthood and a process of de-differentiation in the later part of life, was tested on eighty Israeli participants, age sixteen to seventy-eight. They were asked to divide the course of life into periods, starting at age eleven, and to mark the range of each period. As hypothesized the younger people perceived the lifespan as more differentiated (divided into more periods) whereas older people perceived it in a less differentiated way. There was consensus among the different age groups in their perception of the different stages of development. The earlier stages were viewed as more differentiated whereas the later periods were viewed in a more global way. In addition, women tended to perceive the lifespan as somewhat more differentiated than men; they also tended to perceive the pace of life as more rapid.

Adolescent↗

PubMed1979

Increase in lifespan of rats following polypeptide pineal extract treatment.

The 20 month-long treatment of female rats with daily doses of 0.1 or 0.5 mg of polypeptide pineal extract (PPE) per animal increased their lifespan by 10 and 25%, respectively, as compared with controls. At the age of 16--18 months, 38% of control rats exhibited persistent disturbances in estral function (constant estrus or repeated pseudogestations), whereas these disorders were observed in 7% of experimental animals only. After administration of PPE to 16--18 month-old female rats checked for sterility by a two-week mating, a second mating period resulted in gestation development in four out of 16 animals and deliveries, accordingly. While chronic treatment with PPE did not affect the rate of neoplasm incidence, the mean age of tumour detection in the control group was 697 days and in experimental groups it was 811 and 868 days, respectively. Certain aspects of the interrelationship of rate of ageing, lifespan and specific age pathology are discussed.

Animals↗

PubMed1977

Extension of the lifespan of cultured normal human diploid cells by vitamin E: a reevaluation.

Previously we reported [Packer, L. & Smith, J.R. (1974) Proc. Natl. Acad. Sci. USA 71, 4763-4767] that the lifespan of WI-38 human diploid fibroblasts in vitro was significantly increased by continuously growing the cell cultures in the presence of vitamin E(dl-alpha-tocopherol), but in 19 subsequent subcultivation series we were unable to reproduce these findings. While vitamin E is incorporated into the cells and is able to act effectively as an antioxidant, apparantly is intracellular antioxidant properties alone do not routinely result in an increase of cell lifespan. A synergism between vitamin E and some component(s) in the first of two lots of serum used in the original experiments seems the most likely explanation for our earlier findings.

Cell Division↗

PubMed2025

The DREAM complex links somatic mutation, lifespan, and disease.

The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM activity and somatic mutations across a single-cell atlas of 21 mouse tissues shows that cellular niches with lower DREAM activity have decreased mutation rates. Second, DREAM activity predicts the varied lifespans observed across 92 mammals, with low activity marking longer-lived species. Third, reduced DREAM activity in Alzheimer's patients predicts late disease onset and decreased risk for severe neuropathology. Finally, we show DREAM knockout protects against mutation accumulation in vivo, reducing single-base substitutions by 4.2% and insertion/deletions by 19.6% in brains of mice. These findings position DREAM as a key regulator of aging.

Journal Article↗

PubMed1977

The measurement of red cell lifespan using 59Fe.

Red cell lifespan has been measured using 51Cr and 59Fe in 19 patients. 59Fe can be used to give results which agree closely with those obtained using 51Cr provided that the plasma 59Fe clearance curve is properly defined and the data analysed correctly. In some patients elution of 51Cr may be more than three times the normal level and the use of 59Fe may provide the only reliable estimate of red cell lifespan.

Chromium Radioisotopes↗

PubMed1978

Platelet lifespan in normal pregnancy as determined by a nonradioisotopic technique.

A nonradioisotopic technique for determination of platelet lifespan was applied to 19 healthy women whose gestational ages were between 32 and 40 weeks. Nine non-pregnant women and five men were also studied. Platelet counts were performed in all subjects. No significant difference was demonstrated between platelet lifespan in pregnant women (9.2 days), in non-pregnant women (9.7 days) and in men (9.2 days). There was no significant different between platelet counts in men and in non-pregnant women, but the mean number of platelets in pregnant women was significantly lower. It is concluded that no significant changes in platelet behaviour appear to occur in normal pregnancy.

Adult↗

PubMed2026

17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.

Estrogens are pleiotropic hormones that regulate reproductive and non-reproductive physiological processes in both sexes. Among these, 17α-estradiol (17α-E2), a C17 epimer of the canonical estrogen 17β-estradiol (17β-E2), has emerged as a promising modulator of aging and metabolism with sexual dimorphism. Unlike 17β-E2, which exerts broad estrogenic effects in both sexes, 17α-E2 extends lifespan and preferentially improves metabolic homeostasis in male mice while inducing only mild feminizing effects. Many of these benefits are mediated through estrogen receptor alpha (ERα). However, it remains unknown if its biological actions are mediated through genomic or nongenomic pathways and what the molecular basis is for male-biased efficacy. This review outlines evidence from preclinical models and translational studies, demonstrating that 17α-E2 mitigates age-related metabolic declines in males by reducing adiposity, enhancing insulin sensitivity, and preserving hepatic metabolic plasticity. Elucidating the sexually divergent actions of 17α-E2 can advance our understanding of sex-biased endocrine signaling and how these pathways modulate aging in a sex-specific manner.

Animals↗