Aging & Longevity

Aging-associated loss of chromatin compaction is linked to derepression of retrotransposable elements (RTEs) in mouse and human tissues. Whether such RTE transcription contributes to the microglia activation that is common in aged brains is unknown. Here, we show that DAXX, a histone chaperone and RTE repressor, is downregulated during aging, preserves microglia homeostasis and inhibits cellular senescence. Loss of Daxx in young-adult microglia drives a reactive phenotype marked by chromatin...

Metabolic aging underlies a cluster of chronic conditions-type 2 diabetes, cardiovascular disease, sarcopenia, and neurodegeneration-that account for a substantial share of global morbidity and mortality. A common feature is progressive mitochondrial dysfunction: impaired bioenergetics, disrupted quality control, and loss of metabolic resilience. Reduced mitochondrial DNA copy number in peripheral blood leukocytes is associated with cardiometabolic disease and mortality, but pre-analytical...

Macroautophagy/autophagy is a critical cellular degradation pathway essential for neuronal proteostasis and synaptic function. Its decline with aging is associated with synaptic dysfunction and reduced circuit resilience. NPY (neuropeptide Y), a highly abundant brain neuropeptide, has emerged as an important regulator of autophagy and aging-related processes. In Drosophila, the NPY-family peptide sNPF modulates age-related changes in presynaptic architecture via non-cell autonomous mechanisms....

Neuromodulation techniques in the gamma frequency range, such as chronic 40 Hz sensory stimulation, have gained attention for their potential to impact and preserve cognitive function in the context of neurodegenerative disorders such as Alzheimer's disease (AD). This hypothesis and theory article aims to examine the overlap in biological phenotypes between gamma stimulation techniques and to propose a theoretical mechanism of action that may help to inform future empirical investigations. In...

Age is the primary risk factor for neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, which are characterized by profound loss of midbrain dopaminergic neurons and basal forebrain cholinergic neurons, respectively. In addition, loss of these neurons can occur even in "normal" (i.e., non-pathological) aging, and as a result there is growing recognition of the value of aged animals in studying both normal aging and age-related neurodegenerative disease. The Fischer...

CONCLUSION: Physical performance impairment is strongly associated with balance disorders among older adults, and this relationship is influenced by sociodemographic factors. These findings suggest that sociodemographic characteristics should be considered when evaluating the relationship between physical performance and balance disorders in older adults.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease lacking clarity on the mechanisms linking epithelial injury to fibrotic remodeling. Here, we identify the microbiota-derived corisin as a potent, multifaceted driver of epithelial injury and pulmonary fibrosis. Leveraging targeted DNA sequencing of bronchoalveolar lavage fluid, we provide the first sequence-based identification of corisin in IPF patients and show that functional depletion of native corisin from patient...

Protein restriction extends lifespan across species and engages many hallmarks of aging. We propose that these diverse responses can be understood as components of a single coordinated physiological state. This response involves both cellular nutrient sensing and endocrine and neural coordination, with enhanced longevity emerging from this adaptive response.

Ovarian aging may contribute to systemic aging via the ovarian-systemic axis. This review outlines intrinsic ovarian cellular defects such as genomic instability, epigenetic shifts, and mitochondrial and proteostasis damage, which may trigger senescence-associated secretory phenotype (SASP)-related inflammaging, fibrosis, and distal pro-aging signals. Ovarian-derived endocrine disruption, especially estrogen decline, broadly affects bodily physiology. We summarize emerging multimodal...

Cellular senescence and immune dysfunction intersect as central biological processes shaping disease progression and therapeutic responses across ageing-related pathologies. Rather than acting independently, senescent cells (SnCs) and immune cells engage in a dynamic and bidirectional crosstalk that influences immune surveillance, inflammatory signaling, and tissue remodeling. This review focuses on the molecular and cellular mechanisms through which SnCs modulate immune composition and...

Ageing destabilizes metabolic and neuronal regulatory networks, increasing vulnerability to type 2 diabetes (T2D) and neurodegenerative disorders. These conditions are not independent disease entities but interconnected manifestations of accelerated neuro-metabolic ageing, driven by convergent impairments in insulin signaling, nutrient sensing, mitochondrial bioenergetics, redox homeostasis, proteostasis, and chronic inflammation - processes mediated through conserved hubs including AMPK, mTOR,...

Aging remodels compartmentalized nicotinamide adenine dinucleotide (NAD⁺) circuits in ways that influence stress responses, senescence, tissue repair and susceptibility to fibrosis. Beyond its classical role as a redox cofactor, NAD⁺ fuels sirtuins, PARPs and CD38, linking cellular metabolism to chromatin remodeling, DNA repair, calcium signaling and cell fate. A central translational question is whether modulating NAD⁺ in a given tissue and time window will favor regeneration, restrain fibrotic...

Aging is influenced by both genetic and environmental factors, yet comparative studies across species with different natural lifespans remain limited. We examined how reduced ambient temperature (18 °C vs 25 °C) and constant darkness, compared with a 12 h light/12 h dark cycle (DD vs LD), affect lifespan, age-related physiological traits, and gene expression in three Drosophila species with contrasting natural lifespans and climatic adaptations (tropical, short‑lived D. kikkawai, tropical,...

Caloric restriction (CR) has shown the potential to extend lifespan and reduce cancer risk; however, the mechanisms underlying CR-mediated tumor suppression are not fully understood. Here, we investigate age-dependent CR effects on tumor progression and anti-tumor immune responses in a murine CR model. In aged mice, CR, defined as a 30% reduction in caloric intake, significantly suppressed tumor growth in murine syngeneic models of colorectal cancer or melanoma. CR also enhanced tumor...

: Background: Mitochondrial dysfunction serves as a fundamental driver of the aging process, precipitating progressive functional decline through complex molecular cascades. Summary: This review elucidates the core mechanisms underpinning this dysfunction, including reactive oxygen species (ROS)-induced redox imbalance, mitochondrial DNA (mtDNA) damage accumulation, impaired mitophagy, and metabolic reprogramming. Crucially, we examine how mitochondria act as signaling hubs for inter-organ...

Hepatic fibrosis is a central pathological driver of chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease, which collectively impose a growing global health burden. Fibrosis is primarily mediated by persistent activation of hepatic stellate cells (aHSCs) and excessive deposition of stiff extracellular matrix (ECM). The dense and rigid ECM-aHSCs network severely hinders drug delivery and penetration, posing a major challenge...

Cell therapies represent a promising frontier in modern medicine. Mesenchymal stromal cells (MSCs) constitute a valuable source due to their minimal ethical concerns, low immunogenicity, negligible tumorigenicity in vivo, and robust paracrine activity mediated by the secretion of anti-inflammatory and angiogenic factors. Despite these advantages, MSCs undergo rapid replicative senescence accompanied by a progressive loss of stemness markers and functional potency. In this context, cellular...

CONCLUSIONS: Better cognitive function was associated with higher objective financial literacy, whereas subjective financial literacy showed no association with cognitive performance. These findings highlight the importance of cognitive function for financial literacy in later midlife to early older age adults.

Ischemic postconditioning (I/Post), which is an effective intervention by activating endogenous cardioprotective pathways, recovers ischemia/reperfusion injury. However, this intervention is not as effective in older patients, and its mechanism needs to be further investigated. In this study, we found that myocardial telomeric repeat binding factor 2 (TRF2) protein expression in male aged mice (18 months of age) was lower than that in male adult mice (4 months of age). After ligation of the...

Adipose tissue senescence is increasingly recognized as a key driver of systemic aging and age-related functional decline, yet the endocrine regulators that actively promote this process remain poorly defined. Angiopoietin-like protein 8 (ANGPTL8) is a metabolic factor implicated in lipid metabolism and inflammation and has been associated with multiple aging-related disorders. However, its direct role in adipose tissue senescence and organismal aging remains unclear. Here, we identify ANGPTL8...