Aging & Longevity

Mitochondria are essential for brain energy metabolism and are increasingly recognized as key contributors to brain aging. Although neurons are exceptionally vulnerable to age-related mitochondrial decline, emerging evidence reveals that glial and vascular cells also exhibit distinct mitochondrial impairments. This review synthesizes recent advances in our understanding of mitochondrial dysfunction across specific brain regions and diverse cell types, highlighting subcellular...

Cellular senescence drives aging and disease largely through the senescence-associated secretory phenotype (SASP), yet its regulatory mechanisms remain unclear. Using a SASP reporter combined with a CRISPR-Cas9 screen targeting active regulatory elements, we identify the zinc-finger protein ZNF512B as a key suppressor of the SASP. ZNF512B loss induces DNA damage, activates cGAS-STING signaling, and triggers inflammatory transcriptional reprogramming. In contrast, ZNF512B promotes preferential...

The extracellular matrix (ECM) is a dynamic structural network that supports tissue architecture and regulates cell function. It is primarily composed of collagens, elastin, proteoglycans, and glycoproteins, which are produced by canonical and non-canonical ECM-producing cells. During aging, the ECM undergoes progressive changes in structure and composition, a process recently recognized as the 13th hallmark of aging. In skeletal muscle (SKM), age-associated ECM remodeling, largely regulated by...

Evolution has given rise to lifespans in extant species ranging from days to centuries. Given that mechanisms of ageing are highly conserved, studying long-lived lineages across the animal kingdom could yield insights relevant for healthy ageing in humans. The long lifespans reported for the Heliconius butterfly genus position it as a promising new model system for such studies, but its potential is limited by a paucity of available data. Here, we collate data from commercial butterfly houses,...

The accumulation of mitochondrial DNA (mtDNA) deletion mutants in post-mitotic cells is a hallmark of mammalian ageing and a key contributor to tissue decline in skeletal muscle and neurons. A transcription-coupled replication model predicts that deletions affecting a negative feedback mechanism gain a selective replication advantage, leading to relatively short accumulation times for mutant takeover. However, these accumulation times are experimentally inaccessible since single-cell...

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Whether metabolites enriched at early developmental stages affect cellular and organismal aging remains unclear. In this study, we comprehensively profiled the metabolic landscape of mouse oocytes in comparison to cleavage-stage embryos. Our analysis revealed that oocytes display accumulation of reductive metabolites that diminish following fertilization. Notably, we identified serotonin (5-hydroxytryptamine, 5-HT) as an oocyte-enriched metabolite with protective roles in aging. The underlying...

Cellular senescence contributes to inflammaging in part through the senescence-associated secretory phenotype (SASP). R-loops, three-stranded nucleic acid structures, contribute to innate immune response in cancers; however, the role of R-loops in senescence and inflammaging remains largely unknown. Here we show that nuclear-derived cytoplasmic R-loops promote the SASP and inflammaging. We detect an accumulation of nuclear-derived R-loops in the cytoplasm of senescent cells with an enrichment in...

Intrinsic capacity (IC) is a key construct within the healthy ageing framework. However, the correlations among IC domains and their association with health outcomes in very old adults remain unclear. This study aimed to characterise the relationships among IC domains using network analysis and to examine their association with mortality in community-dwelling octogenarians from the Invecchiamento e Longevità nel Sirente (ilSIRENTE) cohort. IC was calculated as a summary score rescaled to a 0-100...

Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, yet sensitive behavioral and neural markers of early cognitive decline remain to be fully characterized. Increasing evidence suggests that instability of proactive control mechanisms, rather than generalized slowing, may play a critical role in early cognitive impairment. The present study investigated whether behavioral variability and preparatory neural activity constitute neurobehavioral markers...

Cardiovascular-Kidney-Metabolic (CKM) syndrome is uncharacterized in Chinese adults across ages, including centenarians. From three cohorts, age- and sex-standardized CKM prevalence showed nearly 90% stage≥1 and >18% advanced. Prevalence rose with age; advanced CKM reached 100% in male centenarians. Age, sex, smoking, and BMI were risk factors for advanced CKM, with faster male progression. These findings highlight growing disease burden in China's aging population and inform future CKM...

Aging clocks are tools that quantify biological aging through the integration of multi-omics data, encompassing epigenetic, transcriptomic, proteomic, metabolic, and microbial information, together with functional biomarkers. These tools show significant potential for use in preventive medicine, early detection of chronic conditions, and monitoring the effectiveness of interventions designed to enhance population health. The advancement of artificial intelligence has facilitated the widespread...

Despite the effectiveness of combined antiretroviral therapy (ART), HIV infection remains a chronic condition characterised by persistent inflammation and immune activation, likely associated with viral persistence and other factors such as cytomegalovirus (CMV) co-infection. Long-acting (LA) injectable formulations, a newer class of ART with improved and sustained bioavailability, may help modulate the HIV-associated immunoinflammatory state. Therefore, we analysed dynamic changes in lymphoid...

The growing burden of aging-related disease and functional decline across Europe underscores the urgent need to optimize aging trajectories rather than simply extend lifespan. Achieving this goal requires identifying modifiable determinants that shape biological, psychological, and functional aging across the life course. Satisfaction with life (SWL) is emerging as one such integrative factor, linking adaptive capacity, resilience, and long-term healthspan outcomes. In this conceptual and...

Transcription by RNA polymerase II (RNAPII), which is essential for protein-coding gene expression and cellular function, is increasingly understood to become dysregulated with aging. Here, we use a multimodal approach to comprehensively characterize age-dependent changes in RNAPII-mediated transcription in both mouse and human tissues. Short-read total RNA sequencing (RNA-seq) to profile nascent transcription reveals a global reduction in overall transcriptional activity/frequency in aged...

Microbiota-derived metabolites are central mediators between commensal microbes and host immune system at mucosal barrier surfaces. Insights from mouse models have revealed precise molecular mechanisms by which numerous metabolites, including short-chain fatty acids, tryptophan catabolites and bile acid derivatives, regulate epithelial integrity, innate immune tone, and adaptive immunity and tolerance. Parallel studies in humans increasingly confirm these pathways and link metabolite...

CONCLUSIONS: In the multimorbidity management model for older adults, interventions such as patient peer support groups and case manager-led health education are proposed as theoretical strategies. These potential measures aim to support patient self-efficacy and facilitate health literacy, thereby potentially contributing to better overall health of patients.

CONCLUSIONS: There are distinct joint trajectories of physical frailty and social relationships among Japanese community-dwelling older adults. These trajectories are associated with different risks of long-term care needs, with the progressive frailty and rapid social relationships decline subgroup facing the greatest burden.

Macrophages are pivotal immune cells due to their phagocytic capabilities, yet the impact of aging on macrophage phagocytosis remains poorly understood. Using comprehensive in vitro and in vivo phagocytic assays, we demonstrate significantly reduced phagocytic activity in monocyte-derived macrophages from aged humans and mice compared to young counterparts. RNA-seq analysis revealed upregulated expression of extracellular matrix protein genes, particularly collagens, in aged macrophages;...

Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various...