Aging & Longevity

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...

The nature of aging remains debated: is it the accumulation of damage or by execution of a program? Here, we revisit this long-standing dichotomy in light of recent experimental advances, each one of us supporting one of those paradigms and being critical about the other. The damage-driven model views aging as the progressive loss of function caused by imperfect repair and modulated by factors such as rate of damage accumulation, damage resistance, biological redundancy, and tissue regeneration....

How aging of human neurons affects dynamics of essential organelle such as mitochondria and autophagosomes remains largely unknown. MicroRNA-induced directly reprogrammed neurons (miNs) derived from adult fibroblasts retain age-associated signatures of the donor, enabling the study of age-dependent features in human neurons, including longitudinal isogenic samples. Transcriptomic analysis revealed that neurons derived from elderly individuals are characterized by gene expression changes...

Ocular measures are increasingly used as non-invasive proxies of cognitive processes such as attention and listening effort. However, their interpretation in aging populations is complicated by concurrent changes in ocular physiology and oculomotor control, raising a critical question: to what extent do age-related differences in these measures reflect cognitive rather than other physiological factors? Here, we dissociate these contributions by characterizing ocular dynamics (resting and...

CONCLUSION: Higher baseline RCII is consistently associated with both greater baseline frailty and is also associated with steeper frailty trajectories in older adults. These findings suggest that RCII may serve as a valuable biomarker to identify older adults at high risk for functional decline.

INTRODUCTION: Population aging poses significant societal and health challenges, with loneliness and social isolation (L/SI) recognized as pressing public health concerns. While social isolation refers to an objective lack of social contacts, loneliness reflects the subjective perception that one's social needs are not being met. Although L/SI have been associated with an increased risk of dementia and global cognitive decline, their relationship with language functioning remains largely...

Aging is a complex biological process. The corticotropin-releasing factor (CRF) signaling pathway has gained increasing attention for its potential role in regulating aging, acting as a key bridge connecting neuroendocrine stress mechanisms with both central and peripheral aging processes. As a core neuropeptide of the stress response, CRF primarily mediates downstream effects through its type 1 receptor (CRFR1), while its type 2 receptor (CRFR2) may play a modulatory, often opposing, role....

CONCLUSIONS: The flexible Choose Home model successfully fills a gap in the home and community-based care continuum by providing time-limited, high-intensity case management to rapidly stabilize multicomplex older Veterans. This sustainable, provider-led interprofessional approach offers a scalable strategy to support aging in place and reduce costly institutional care.