Biogerontology最新文献

Telomere length (TL) is a well-established biomarker of biological ageing, sensitive to cumulative physiological and psychosocial stress. This review synthesises current evidence on how pregnancy, postpartum stressors, and reproductive history shape maternal biological ageing, integrating findings from telomere biology and emerging epigenetic ageing measures. Pregnancy represents a period of substantial metabolic, hormonal, and immunological demand and is increasingly conceptualised as a transient state of accelerated biological ageing. While telomere shortening is not consistently detectable during gestation, epigenetic clocks indicate a temporary increase in biological age, which is only partially reversible postpartum. Across the life course, higher parity is associated with shorter TL, with evidence suggesting a cumulative effect that becomes most apparent in later life and around the menopausal transition. However, this relationship is heterogeneous and modified by factors including age at last birth, breastfeeding, and socioeconomic context. Postpartum represents a critical and underexplored window in which sleep deprivation, psychological stress, and social factors converge to influence telomere dynamics. In particular, poor sleep quality and postpartum depression (PPD) are consistently linked to accelerated telomere attrition and epigenetic ageing, with emerging evidence of a bidirectional relationships whereby shorter TL may also predispose to PPD. Overall, evidence supports a model in which reproductive events impose are associated with measurable transient and cumulative costs to cellular ageing biomarkers. These findings highlight the importance of incorporating postpartum health, particularly sleep and mental health support, into life-course models of ageing and underscore the need for longitudinal, mechanistic, and intervention-focused research in maternal populations.

Aging is a multifactorial process affects different tissues and organs and is modulated by genetic and environmental factors. In aging, the frequency of DNA repair errors and genomic instability are augmented. Depletion of endogenous antioxidant capacity during aging promotes the development of oxidative stress which triggers oxidative stress-induced DNA injury. Brain aging is manifested by cognitive impairment and memory disorders. Development of neuronal senescence is the major pathway in the progression of brain aging. Silent information regulator sirtuin 1 (SIRT1) is a class III histone deacetylase plays a critical role in genomic stability during aging. SIRT1 is highly expressed in specific brain regions involved in energy expenditure and metabolic activity that is necessary for brain development and control of brain senescence. Therefore, SIRT1 may have neuroprotective effects against brain aging and related neurodegenerative diseases. This narrative review aims to critically evaluate the role of SIRT1 in brain aging and to summarize current evidence on compounds that directly or indirectly modulate SIRT1 activity, with a focus on their mechanistic pathways and potential therapeutic implications. Findings of the present review highlighted that SIRT1 activators such as resveratrol, metformin and statins have neuroprotective effects against brain aging by regulating inflammatory and oxidative stress disorders through modulation of downstream signaling pathways.

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.

Background: Chronic morphine consumption induces oxidative stress and renal dysfunction, effects that may be exacerbated by aging-related declines in adaptive capacity. Regular endurance exercise enhances antioxidant defense and mitochondrial regulation; however, its ability to counteract morphine-induced renal alterations across different stages of aging remains insufficiently characterized.

Methods: Male wistar rats, categorized as young and aged based on chronological age and body weight, were allocated to control, morphine, exercise, and morphine plus exercise groups within each age category. Morphine was administered via drinking water for four weeks. Concurrently, animals in the exercise groups performed moderate-intensity continuous training on a treadmill. At study completion, serum and renal tissues were collected for assessment of oxidative stress markers (MDA, TAC, SOD), MPO, renal function indices (BUN and creatinine), and renal expression of sirtuin 1 (SIRT1) and Klotho, Mitochondrial compatibility markers (Citrate synthase activity and TFAM).

Results: Chronic morphine exposure was associated with increased oxidative stress markers and decreased antioxidant capacity in kidney tissue, and simultaneously increased serum urea and creatinine levels in young and old mice, indicating impaired renal functional status. Chronic morphine administration also decreased SIRT1 and Klotho levels in young and old animals. In contrast, 4 weeks of endurance training improved markers of mitochondrial adaptation, oxidative balance, and renal function, which were associated with increased expression of SIRT1 and Klotho in kidney tissue. These changes could indicate a potential link between exercise training and molecular pathways involved in the regulation of oxidative stress and renal homeostasis. However, these findings suggest an association, and causal or mechanistic interpretations will require further investigation in future studies.

Conclusion: These findings indicate that endurance training is associated with more favorable renal biomarker profiles in the context of chronic opioid exposure.

Aging-related neurological disorders, including stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and various neuroinflammatory conditions, affect over three billion individuals worldwide and constitute leading causes of morbidity, disability, and socioeconomic burdens. Aging contributes not only to the increased incidence of these disorders but also to their progression through interconnected mechanisms, including endothelial dysfunction, oxidative stress, chronic inflammation, mitochondrial dysfunction, cellular senescence, metabolic imbalance, and gut microbiota dysbiosis. These processes collectively impair neuronal survival, synaptic plasticity, and cognitive and motor functions. Traditional Chinese medicine (TCM), with its characteristic multi-component and multi-target therapeutic strategies, has emerged as a promising approach to counteract age-associated neurological decline. Accumulating preclinical studies suggest that TCM interventions may exert neuroprotective, anti-inflammatory, and antioxidant effects, modulate autophagy, restore metabolic homeostasis, and potentially delay cellular senescence. However, high-quality clinical evidence on safety and efficacy remains limited. This review summarizes current insights into the molecular interplay between aging and neurological disorders and highlights the therapeutic potential of TCM in targeting hallmarks of aging, providing perspectives for integrative prevention and treatment strategies for neurodegenerative and neurovascular diseases.

Endothelial senescence is a critical contributor to vascular aging and age-related vasculopathies. Our previous work identified AGGF1 as a regulator of cell cycle progression and anti-inflammatory signaling. However, whether AGGF1 modulates endothelial senescence remains unclear. Here, we demonstrate that AGGF1 is downregulated in both replicative and DOX-induced senescent HUVECs. AGGF1 knockdown accelerated cellular senescence as evidenced by senescence markers, including increased SA-β-gal activity, enhanced formation of γH2AX foci, elevated IL-6 levels, and impaired proliferation, whereas AGGF1 overexpression prevented DOX- and MMC-induced senescence using adenovirus and lentivirus-mediated gene manipulation. To investigate the underlying mechanisms, we performed RNA sequencing, small-molecule drug intervention, transmission electron microscopy (TEM), and other imaging techniques in subsequent experiments. Transcriptomic and functional analyses revealed that AGGF1 transcriptionally upregulates TGFB3, which is associated with TAK1 activation and AMPK phosphorylation, ultimately inhibiting excessive mitochondrial fragmentation and suppressing cellular senescence. This signaling module reduced DRP1 expression and attenuated its activating phosphorylation at Ser616. TEM results further confirmed that AGGF1 overexpression significantly reduced mitochondrial fragmentation in cells. Additionally, this proposed association was supported by pharmacological inhibition (Takinib, Compound C) and TGFB3 knockdown, which abrogated AGGF1-mediated protection. Collectively, we identified that AGGF1 is critical for regulating a proposed TGFB3-TAK1-AMPK regulatory module, which delays endothelial senescence partially through maintenance of mitochondrial morphology. Our study provides evidence that AGGF1 plays an important role in metabolic control and cellular senescence.

Age is a major risk factor for cardiovascular disease, yet the molecular mechanisms underlying human cardiac aging are not fully understood. Using bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) project, we identified cardiac age-associated genes by intersecting transcripts significantly correlated with age in both the atrial appendage and left ventricle, while excluding those similarly altered in skeletal muscle. Among these, 131 genes were positively correlated with age, and 262 were negatively correlated. Functional enrichment and gene set enrichment analyses revealed several recurring biological themes. Pathways positively enriched with age included the P53 pathway, replicative senescence, extracellular matrix organization, transient receptor potential channel activity, and cardiac epithelial-mesenchymal transition. Conversely, negatively enriched pathways involved fatty acid oxidation, oxidative phosphorylation, mitochondrial biogenesis, membrane repolarization, cardiac conduction, and NOS1 signaling. Immune deconvolution indicated an age-dependent increase in neutrophil fractions and a decrease in monocyte abundance. Finally, an ordinal elastic net regression model, trained on these cardiac age-associated genes, demonstrated acceptable internal performance, achieving a quadratic weighted kappa of 0.797 and an ordinal concordance index of 0.901. External validation on two independent microarray cohorts showed modest predictive capability, with R² values of 0.20 and 0.38. These findings provide a transcriptomic landscape of cardiac aging based on human tissue, with potential implications for biomarker development and therapeutic strategies.

Satellite cells (SCs) are essential for skeletal muscle regeneration, but their function declines with aging, often associated with increased pro-apoptotic signaling. This study investigated the impact of in vitro serum starvation-as a model of acute microenvironmental and nutrient stress-on the apoptosis and differentiation potential of human SCs from young and aged donors. SCs were isolated from the Vastus Lateralis of young and aged subjects and cultured in serum-free medium for up to 72 h. We assessed apoptosis through Annexin V/PI staining, TUNEL assays, and caspase activity measurements, while transcriptional profiles were analyzed via RT-PCR. Aged SCs displayed a significantly higher susceptibility to stress-induced apoptosis compared to young controls, marked by the early upregulation of CASP9 and FOXO1. While typical nucleosomal DNA fragmentation was absent, we observed the activation of caspase-3 after 72 h of starvation. In aged cells, activated caspase-3 co-localized with myogenin and extranuclear DNA at sites of nuclear remodeling. Notably, treatment with a pan-caspase inhibitor (z-VAD-fmk) prevented the formation of micronuclei and myotubes, further highlighting a non-apoptotic role for these enzymes. Aged SCs also showed a distinct cell cycle profile characterized by an enlarged G0/G1 phase and altered expression of CDK and CCNB1 genes. Our findings suggest that in human aged SCs, caspase enzymes serve a dual role: mediating a heightened stress response and facilitating the nuclear remodeling necessary for myogenic differentiation. These results clarify how intrinsic aging shapes the response of muscle stem cells under severe environmental and metabolic resource deprivation.

Cellular senescence is a context-dependent cellular state characterised by persistent cell-cycle arrest, epigenetic remodelling, metabolic reprogramming and acquisition of a senescence-associated secretory phenotype. Transient senescence contributes to embryogenesis, tissue repair and tumour suppression, whereas persistent senescent cell populations accumulate with advancing age across multiple tissues, in part owing to declining immune-mediated clearance and intrinsic resistance to apoptosis, thereby promoting chronic systemic inflammation, tissue fibrosis, stem-cell dysfunction and propagation of secondary senescence. Experimental genetic and pharmacological evidence supports a contributory and in several contexts causal role for senescent cells in cardiovascular, metabolic, musculoskeletal, fibrotic and neurodegenerative disorders. These findings have accelerated the development of senotherapeutic strategies, including senolytics, senomorphics and immune-mediated clearance approaches, with early clinical studies showing preliminary evidence of functional benefit in idiopathic pulmonary fibrosis and diabetic kidney disease. However, clinical translation remains constrained by senescence heterogeneity, limited biomarker specificity and unresolved long-term safety concerns. Improved molecular, spatial and functional resolution of senescent states will be essential for developing biomarker-guided and tissue-specific interventions that preserve the beneficial functions of transient senescence while limiting its chronic deleterious effects.