Biogerontology最新文献

If a shortened lifespan is evolutionarily advantageous, it becomes more likely that nature will strive to change it accordingly, affecting how we understand aging. Premature mortality because of aging would seem detrimental to the individual, but under what circumstances can it be of value? Based on a relative incremental increase in fitness, simulations were performed to reveal the benefit of death. This modification allows for continuous evolution in the model and establishes an optimal lifespan even under challenging conditions. As a result, shorter-lived individuals achieve faster adaptation through more frequent generational turnover, displacing longer-lived ones and likely providing a competitive advantage between species. Contrary to previous assumptions, this work proposes a mechanism by which early death, e.g., due to aging, may contribute to evolution.

Human populations are experiencing unprecedented growth and longevity with lingering knowledge gaps of the characteristics, mechanisms, and pathologies of senescence. Invasive measurements and long-term control conditions for longitudinal studies are infeasible, necessitating the need for surrogate animal models. Rats have short lifespans (2-3 years) with translatable cardiovascular systems, and Sprague Dawley microcirculatory preparations are key to studying the oxygen transport mechanisms critical to the loss of skeletal muscle function in aging. Here we present baseline physiological data of 61 male, Sprague Dawley rats at 3, 6, 12, 18, and 24 months of age. Anesthetized animals were surgically prepared for femoral arterial and venous cannulations, tracheal intubation, and exteriorization of the spinotrapezius muscle. Measurements included cardiovascular function, blood gases, and peripheral tissue interstitial oxygen tension (P_ISFO₂) using phosphorescence quenching microscopy. Intrinsic heart rates decreased with age without significant changes to blood pressure. Arterial oxygen tension declined 17% by 18 and 24 Months (p < 0.05) while p_ACO₂ and P_ISFO₂ were unchanged. Lactate was elevated at 12 and 18 Months along with an alkaline shift in blood pH. Heart rate and decreased p_AO₂ decoupled from p_ACO₂ are conserved phenomena in human aging. The continuity of resting P_ISFO₂ despite an anaerobic shift in metabolism may be due to declining mitochondrial function and dysregulation of the vascular response to hypoxemia, which are also present in aged humans. These physiological and microcirculatory data offer a useful experimental model for investigating the detailed changes in oxygen supply and demand that affect senescing skeletal muscles in rats and humans.

The capacity for tissue repair during wound healing declines with age. A chronic low but systemic inflammatory status, often called "inflammaging", is considered a key factor that contributes to impaired tissue regeneration. This phenomenon has been substantiated by an increased number of immune cells in wound-tissue of old mice. Although immune cells coordinate an inflammatory response by their secretome the composition of the wound milieu has not been examined. In young (2 months) and old (18 months) female mice, excision wounds were induced using a punch biopsy device, i.e., the healing progress occurred through secondary intention. The closure rate was analyzed for 7 days. At days 1, 3 and 7 post-surgery, wound specimen were investigated for immunohistochemical detection of granulocytes, M1-macrophages and mesenchymal stem cells of the skin. The concentrations of inflammatory cytokines and regenerative growth factors were determined in tissue homogenates by ELISA. The carbonyl assay was used to determine protein oxidation. In old mice, the wound closure was delayed between days 1 and 3 post-surgery, as was the peak of immune cell infiltration. There was no age effect on the concentration of inflammatory cytokines, but wounds of young animals contained higher number of mesenchymal stem cells and increased levels of growth factors. Protein oxidation was increased with age. The present study suggests that a reduced regenerative capacity rather than an enhanced inflammatory score affected the tissue regeneration process in old mice.

Extracellular vesicles (EVs) are implicated in inter-organ communication, which becomes particularly relevant during aging and exercise. DNA methylation-based aging clocks reflect lifestyle and environmental factors, while regular exercise is known to induce adaptive responses, including epigenetic adaptations. Twenty individuals with High-fitness (aged 57.7 ± 9.8 years) and twenty Medium-Low-fitness (aged 57.5 ± 9.7 years) subjects provided blood samples. EVs were isolated from the samples using a size exclusion chromatography (SEC)-based method, and their protein content was analyzed by mass spectrometry (MS). Acceleration of the biological age estimator DNAmFitAge (AgeAccelFit) was associated with the protein cargo of EVs, whereas PhenoAge and GrimAge acceleration did not show a significant relationship. This finding suggests that the epigenetic aging-modulating role of exercise may involve inter-organ communication via EVs. Set Enrichment Analysis was performed to identify enriched Gene Ontology (GO) terms for sets of proteins that were either correlated with AgeAccelFit or detected exclusively in individuals with high levels of aerobic fitness. The protein cargo of EVs further suggests that inter-organ communication influences inflammation, the immune system, cellular repair, adhesion, metabolism and coagulation. Our findings help to understand the preventive role of exercise, which could be mediated in part by EVs.

Over the years, the study of adult sex ratio is a topic that has gained attention for its impact on reproductive outcomes and aging across various insect species. However, there is still limited research focused on insects reared for food and feed production. To address this gap, this study aimed to evaluate the impact of different adult sex ratios on the reproductive dynamics and longevity of the superworm, Zophobas morio (F.) (Coleoptera: Tenebrionidae), a species with interesting potential as a nutrient source. In this study, we assessed three adult sex ratios, i.e., 5:5, 6:4 and 8:2 (female:male) with mesh used to each setup. An additional 5:5 sex ratio without mesh served as control. On a weekly basis, adult survival, egg production, and egg hatching rates were recorded. Our results revealed statistically significant differences in egg production across the different sex ratios tested, but no statistically significant differences in hatching rates and adult survival. These findings suggest that both balanced and female-biased sex ratios are suitable for Z. morio and that it is important to consider this factor when enhancing efficiency in large-scale insect production.

Biomarkers of ageing (BA) can predict health risks beyond chronological age, but little is known about how marital/living status affects longitudinal changes in BA. We examined the association between marital/living status and BA over time using the-Swedish-Adoption/Twin-Study-of-Aging (SATSA) cohort. Four BAs were analyzed: telomere length (TL) (638 individuals; 1603 measurements), DNAmAge (535 individuals; 1392 measurements), cognition (823 individuals; 3218 measurements), and frailty index (FI) (1828 individuals; 9502 measurements). Individuals were born between 1900 and 1948, and data on marital/living status, BAs, and covariates were collected through nine waves of questionnaires and in-person testing from 1986 to 2014. Mixed linear regression with random effects at twin-pair and individual levels were used to assess BA changes for constant marital/living status. Conditional generalized estimating equation assessed within-individual BA changes for varying marital/living status. Results showed that individuals who were consistently unmarried/non-cohabiting (β = 0.291, 95%CI = 0.189-0.393) or living alone (β = 0.203, 95%CI = 0.090-0.316) were more frail, and experienced accelerated frailty (p-for-interaction with age < 0.001 for marital status; p-for-interaction = 0.002 for living status) and cognitive decline (p-for-interaction < 0.001), compared to those married/cohabiting or living with someone Among individuals whose marital/living status changed, frailty was higher when living alone (β = 0.089, 95%CI = 0.017-0.162) and frailty accelerated when they became unmarried/non-cohabiting or were living alone (p-for-interaction < 0.001). Cognitive decline also accelerated when living alone (p-for-interaction = 0.020). No associations were observed for TL and DNAmAge. In conclusion, being unmarried/non-cohabiting or living alone from mid-to-old age is linked to accelerated cognitive decline and frailty. These findings highlight the potential importance of social support networks and living arrangements for healthy ageing.

Mitochondrial DNA encodes essential components of the respiratory chain complexes, serving as the foundation of mitochondrial respiratory function. Mutations in mtDNA primarily impair energy metabolism, exerting far-reaching effects on cellular physiology, particularly in the context of aging. The intrinsic vulnerability of mtDNA is increasingly recognized as a key driver in the initiation of aging and the progression of its related diseases. In the field of aging research, it is critical to unravel the intricate mechanisms underpinning mtDNA mutations in living organisms and to elucidate the pathological consequences they trigger. Interestingly, certain effects, such as oxidative stress and apoptosis, may not universally accelerate aging as traditionally perceived. These phenomena demand deeper investigation and a more nuanced reinterpretation of current findings to address persistent scientific uncertainties. By synthesizing recent insights, this review seeks to clarify how pathogenic mtDNA mutations drive cellular senescence and systemic health deterioration, while also exploring the complex dynamics of mtDNA inheritance that may propagate these mutations. Such a comprehensive understanding could ultimately inform the development of innovative therapeutic strategies to counteract mitochondrial dysfunctions associated with aging.

In cells, the term "cellular aging" represents a collection of biological changes that can precede the proliferative senescence states. Cells more resistant to proliferative senescence, such as the ones found in the basal layer of the epidermis, may also exhibit these aging patterns. Therefore, cellular aging events could be induced by endogenous signals named here as cellular aging triggers (CATs) components. The superoxide anion (O₂⁻) could be a prime candidate for a CATs, as it is continuously produced by eukaryotic cells. To test this hypothesis, mitochondrial and cytoplasmic O₂⁻ imbalances were induced in HaCaT keratinocytes using rotenone (ROT, 30 µM), which inhibits mitochondrial complex I and paraquat (PQT, 30 µM), which increases O₂⁻ levels via redox cycling. ROT and PQT reduced cellular proliferation rate and elevated β-Galactosidase and transforming growth factor beta (TGF-β) levels. Furthermore, they increased the frequency of larger cells with nuclear alterations, the levels of oxidative markers, and interleukin 1β, a marker of the Senescence-Associated Secretory Phenotype (SASP). However, the mitochondrial O₂⁻ imbalance caused by ROT led to more pronounced alterations compared to PQT. These findings support the hypothesis that the existence of CAT components, such as the O2⁻ anion, plays a significant role in cellular aging.

Chronic kidney diseases (CKD) are a group of multi-factorial disorders that markedly impair kidney functions with progressive renal deterioration. Aging contributes to age-specific phenotypes in kidneys, which undergo several structural and functional alterations, such as a decline in regenerative capacity and increased fibrosis, inflammation, and tubular atrophy, all predisposing them to disease and increasing their susceptibility to injury while impeding their recovery. A central feature of these age-related processes is the activation of the p53/p21 pathway signaling. The pathway is a key player in cellular senescence, apoptosis, and cell cycle regulation, which are all key to maintaining the health of the kidney. P53 is a transcription factor and a tumor suppressor protein that responds to cell stress and damage. Persistent activation of cell p53 can lead to the expression of p21, an inhibitor of the cell cycle known as a cyclin-dependent kinase. This causes cells to cease dividing and leads to senescence, where cells can no longer increase. The accumulation of senescent cells in the aging kidney impairs kidney function by altering the microenvironment. As the number of senescent cells increases, the capacity of the kidney to recover from injury decreases, accelerating the progression of end-stage renal disease. This article review extensively explores the relationship between the p53/p21 pathway and cellular senescence within an aging kidney and the emerging therapeutic strategies that target it to overcome the impacts of cellular senescence on CKD.

The aging population faces a gradual decline in physical and mental capacities, with an increased risk of liver cirrhosis and chronic liver diseases leading to hepatic encephalopathy (HE). The intertwining of physiological manifestations of aging with the pathophysiology of HE significantly impairs cognitive ability, reduces quality of life, and increases mortality. Hence, effective therapeutic intervention is imperative. The present study investigated the impact of minimal HE (MHE) on cognitive impairment in an aged rat population by analyzing hippocampal proteome dynamics. For this purpose, an old MHE rat model was induced via thioacetamide. The label-free LC‒MS/MS method was employed to explore hippocampal proteomic changes and associated dysregulated biological pathways. A total of 1533 proteins were identified, and among these, 30 proteins were significantly differentially expressed (18 upregulated, and 12 downregulated). Three upregulated proteins, namely, fetuin-A, p23, and intersectin-1 were selected and validated for their increased expression via western blotting and immunofluorescence analysis, which confirmed the mass spectrometry results. These proteins have not been reported previously in MHE cases. We also identified the possible dysregulated biological pathways associated with the differentially expressed proteins via Metascape, a network analysis tool. We found that the differentially expressed proteins may be involved in the generation of precursor metabolites and energy, the neurotransmitter release cycle, positive regulation of dendritic spine development, chaperone-mediated protein folding and protein stabilization. This study highlights the potential mechanisms underlying neurological dysfunction in the aged population with MHE and identifies novel therapeutic targets for improved disease management.