Aging & Longevity

Metabolic disorders, particularly insulin resistance, are increasingly recognized as accelerators of female reproductive decline. However, the molecular mechanisms by which peripheral metabolic stress translates into impaired ovarian reserve remain incompletely understood. Here, we propose that protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling, serves as a molecular bridge linking systemic insulin resistance to aging-relevant ovarian dysfunction and can be...

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) deposition, tau hyperphosphorylation, and chronic neuroinflammation. Emerging evidence from preclinical models suggests that aberrant immune crosstalk between regulatory T cells (Tregs) and microglia may contribute to disease progression, though its precise role in human AD remains to be fully elucidated. In rodent models, Tregs have been shown to cross the blood-brain barrier and, through cell-contact-dependent mechanisms and...

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Preservation of host fitness is a common feature of longevity and immunity to infection. In this issue of Immunity, Triana-Martinez et al. reveal that p16^(High) senescence-associated immune cells promote disease tolerance and healthy aging. Mechanistically, this is dependent on Toll-like receptor 7 (TLR7) and stimulator of interferon genes (STING) innate immune signaling controlling adenosine concentrations.

All immune cells engage in cholesterol metabolism, which generates a spectrum of bioactive metabolites that mainly include cholesterol itself, its biosynthetic intermediates, and oxidized or sulfated derivatives. These metabolites regulate not only cellular metabolism but also immune signaling. In addition, several functional proteins within cholesterol metabolic pathways exert non-canonical signaling functions that shape immune cell responses. Distinct immune cell types adopt specialized...

The perivascular glymphatic system promotes cerebrospinal fluid-interstitial fluid (CSF-ISF) interaction and macromolecular waste clearance and is an important determinant of brain homeostasis, the performance of which deteriorates with age. Astrocyte biology, vascular integrity, and age-associated cerebrovascular dynamic alterations interfere with the polarization of aquaporin-4 (AQP4) water channels on astrocytic endfeet, decreasing the clearance of aggregation-prone proteins, such as...

Brain aging is associated mainly with a decline in cognitive function and is a major risk factor for various neurodegenerative disorders (NDDs). Major hallmarks of aging include oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and impaired proteostasis. Although caloric restriction (CR) has consistently demonstrated neuroprotective effects, its long-term effects in humans remain challenging. Consequently, CRMs such as metformin, spermidine, and curcumin have been widely...

Cancer is increasingly relevant to ageing societies, yet progress in cancer control is difficult to assess when population years of life lost (YLL) to cancer appear stable. Using Danish registers, we followed 4.26 million residents aged ≥50 years (1980-2019) and estimated YLL under observed and counterfactual scenarios, separating demography and incidence from post-diagnosis outcomes. From the 1980s to the 2010s, YLL per individual changed little (men 2.3 to 2.1; women 2.5 to 2.2), while YLL per...

Aging is a complex multifactorial process that affects cellular function and tissue homeostasis over time. Despite substantial research, the molecular mechanisms driving cellular aging remain poorly understood. Many studies focused on changes in DNA methylation as an indicator of aging. In particular, methylation at polycomb CpG islands was shown to be predictive of phenotypic changes associated with aging. Since many age-related pathological processes are thought to originate from single cells,...

Aging is accompanied by progressive physiological decline and an increased risk of chronic disease, motivating the search for interventions that promote healthy longevity. We found that mid-life administration of Corylin, a flavonoid derived from Psoralea corylifolia, improves metabolic function, muscle integrity, and physical performance in mice maintained on a standard diet. Corylin significantly extends median lifespan in female mice, with an 11.9% increase and a 33% higher survival rate at...

Chronic inflammation drives vascular aging and stroke risk, yet circulating proteins linking immune activation to cerebrovascular events remain elusive. People with HIV (PWH) face elevated stroke risk beyond traditional vascular risk factors, even under antiretroviral therapy. We aimed to identify circulating proteomic signatures of HIV-associated stroke, characterize underlying biological pathways, and assess their longitudinal stability. We conducted a nested case-control study of 135 PWH with...

Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model-a stochastic model of damage accumulation and removal-and fit it to survival data from well-studied species. Several parameters have...

How the small intestine ages at the cellular and molecular level has been unclear. Here we profile single nuclei from young and aged primate small intestine and find that aging brings barrier dysfunction, chronic inflammation and a shift in stem cell differentiation away from absorptive cells toward secretory cells. Through integrative multimodal analysis, we identify the transcriptional corepressor NCoR1 as a key player whose decline is conserved in the aging human gut. In human intestinal...

Nucleotides-essential substrates for DNA repair, energy metabolism, and redox regulation-are emerging as nutritional modulators of biological aging. Yet, individual responses to exogenous nucleotide (NTs) supplementation remain poorly understood. Given that urate metabolism governs systemic oxidative balance, this study investigated whether genetic variability in urate regulation modifies the anti-aging effects of NTs. In this secondary analysis of the TALENTs randomized controlled trial (121...

Aging reshapes global disease burdens, yet the regulatory roles of long non-coding RNAs (lncRNAs) in age-related disorders remain incompletely characterized. We developed iLDA-SGCN, a graph-based computational framework that integrates singular value decomposition (SVD) with dual graph convolutional networks (GCNs) to predict lncRNA-disease associations. SVD first derives compact low-dimensional representations from the lncRNA-disease association matrix. Two complementary GCN modules then learn...

Excessive alcohol consumption poses significant health risks and is closely associated with oxidative damage. The KEAP1-NRF2-ARE signaling pathway serves as the primary antioxidant system. However, current small molecule inhibitors are all covalently bound to KEAP1, meaning that once bound, they are not easily dissociated, while continuous inhibition of KEAP1 exhibits severe side effects. In this study, BLI, CETSA, Pull-down, Co-IP, and HDX-MS assay analysis were conducted to detect the KEAP1...

CONCLUSIONS: Maintaining favorable long-term patterns of PA, even with gradual decline, is associated with reduced odds of DS among older adults with chronic diseases. These findings support PA as a potentially cost-effective strategy for secondary prevention and highlight the importance of sustained behavioral patterns in mitigating mental health risks in aging populations.

CONCLUSION: Frailty is common among Iranian older adults and is independently associated with poorer physical QoL and, to a lesser extent, mental QoL. These findings support the need for targeted screening and multidomain interventions.

Neurons and glia work together to dynamically regulate neural circuit assembly and maintenance. In this study, we show that Drosophila exhibit large-scale synapse formation and elimination as part of normal CNS circuit maturation and that glia use conserved molecules to regulate these processes. Using a high-throughput ELISA-based in vivo screening assay, we identify new glial genes that regulate synapse numbers in Drosophila in vivo, including the scavenger receptor ortholog Croquemort (Crq)....