Aging & Longevity

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a broad spectrum of molecular alterations that influence clinical outcomes. TP53 mutations define one of the most lethal subtypes of AML, driving resistance to nearly all available treatment modalities, including venetoclax plus azacitidine (VenAza). Yet, the molecular basis of this resistance, beyond affecting transactivation of BCL-2 family genes, has remained elusive. Here, we demonstrate that VenAza treatment leads to...

Biostimulatory dermal fillers are widely used for skin rejuvenation, but how particle physicochemical properties regulate fibroblast-macrophage interactions and collagen remodeling remains unclear. We compared calcium hydroxylapatite (CaHA), polycaprolactone (PCL), spherical poly-L-lactic acid (PLLA-Sp), and irregular PLLA fragments (PLLA-Ir) through comprehensive characterization (SEM, FTIR, zeta potential, AFM, roughness, tapped density, rheology in HA matrices) along with in vitro (human...

Nicotinamide adenine dinucleotide (NAD) is a metabolic cofactor regulating energy metabolism, epigenetics, DNA repair, and signaling. Although NAD declines with vitamin B3 deficiency, disease, and aging, systemic consequences of chronic depletion remain unclear. Here, we characterize an in vivo model of inducible NAD deficiency using acquired niacin dependency (ANDY) mice, in which NAD synthesis becomes dependent on dietary niacin. On a niacin-free diet, ANDY mice developed widespread tissue NAD...

The implementation of CMS age-friendly care initiatives has created new opportunities for geriatricians to shape clinical care, quality improvement, education, and health system strategy. A geriatrician's unique contribution extends beyond managing medical complexity; it lies in applying expertise in aging physiology, functional change, psychosocial context, heterogeneity, prognosis, patient priorities, and ageism to clinical and organizational decision-making. Geriatrics expertise must be...

CONCLUSIONS: This study lays the foundation for developing standardised proxy ageing-in-place indicators to monitor how older people with or at risk of frailty are living in their homes and communities. Future directions include assessing feasibility of capturing non-clinical indicators routinely; applying these indicators to guide personalised targeted interventions; and leveraging technology-related indicators to improve digital inclusion and literacy in older people to support...

CONCLUSIONS: Widowhood exerts a significant positive impact on hospitalization risk among Chinese older adults, with heterogeneous effects across cohorts and calendar time and an immediate but non-persistent dynamic pattern. These findings highlight the need for targeted interventions, particularly during the immediate year following spousal loss and for specific high-risk cohorts. Practical steps include enhancing family-based health management support and optimizing healthcare accessibility...

CONCLUSIONS: In this selected sample, functional fitness, particularly aerobic endurance and lower-limb flexibility, accounted for the largest share of explained variance, whereas EHBMS-assessed beliefs added negligible variance. Because no analysis formally compared predictor domains, this reflects relative incremental contribution, not a tested difference. The null belief findings warrant caution because self-efficacy was unmeasured and several subscales showed ceiling effects.

Genetic trade-offs can constrain life-history evolution resulting in the evolution of ageing. Reduced insulin/insulin-like signalling (rIIS) improves somatic maintenance and dramatically increases lifespan in Caenorhabditis elegans, but the effects on fitness are unclear. Here we used a novel experimental approach to show that, contrary to the prevailing paradigm, rIIS via daf-2 RNAi during development can improve development, reproduction, survival, individual fitness, and population growth...

The growing evidence that existing cardio-renal-metabolic therapies, such as GLP-1 receptor agonists and SGLT2 inhibitors, confer all-cause mortality benefits has positioned them as the first wave of potential gerotherapeutics. However, repurposing these drugs for a lifespan extension indication remains constrained by trial duration, misaligned incentives, and the lack of a viable regulatory path. We highlight two parallel strategies to address these barriers: (1) identifying and validating...

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The steroid hormone dafachronic acid may carry the effects of reduced mTOR activity between tissues to coordinate metabolism and longevity across the body.

Advanced brain age relative to chronological age may predict cognitive decline in healthy aging, but prospective evidence remains limited. We tested whether the brain age gap (BAG) predicts cognition and 5-year cognitive decline in the AGES-Reykjavik Study. Participants with structural MRI and neuropsychological data were included cross-sectionally (n = 4,606); mean age 76.4y; 58% female) and longitudinally (n = 2,561; mean follow-up 5.2y). BAG was estimated from T1-weighted MRI. Mixed-effects...

Cellular senescence is characterized by coordinated disruptions in mitochondrial function and epigenetic regulation, with perturbation of the mitochondria-chromatin axis emerging as a central hallmark of this process. Resveratrol (RSV) has been extensively investigated as a modulator of this axis; however, its clinical utility is constrained by dose-dependent cytotoxicity. Here, we evaluated the safety profile and anti-aging potential of resveratrol glucoside (R-glc), a glucosylated derivative...

Aging is modulated by conserved nutrient-sensing pathways that integrate metabolic cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in...

Cytotoxic chemotherapy typically results in the elimination of a fraction of the tumor with surviving cells entering a state of persistence or premature replicative senescence that can lead to recurrence. Here, we show that therapy-induced senescence is associated with robust up-regulation of Fas and/or TRAIL-R2/DR5 death receptors in vitro and in vivo. The latter receptors restricted entry to senescence and exerted selective pressure on senescent cells through promoting assembly of proapoptotic...

Inflammaging, a state of chronic low-grade inflammation, is a key contributor to biological aging and diabetes. Traditional inflammatory indices within the interplay between inflammation and epigenetic aging have remains insufficiently explored. In addition, novel platelet-based inflammatory indices based on platelets may perform better than traditional inflammatory indices. This study was a cross-sectional study with survival analysis and analyzed data from 2494 participants in the National...

Neuronal senescence, triggered by oxidative stress and inflammatory responses, is a significant risk factor for brain aging, ultimately leading to cognitive decline. Apelin-13, an exercise-induced myokine, exhibits potential neuroprotective effects by the APJ system, but its protective effects against neuronal senescence and the underlying mechanisms are unknown. This study aimed to elucidate how apelin-13 prevents D-galactose-induced neuronal senescence in SH-SY5Ys, human induced pluripotent...

Moderately cold temperatures extend lifespan and promote health across species^(1-3), yet the molecular mechanisms underlying these benefits remain unclear. Here we define a metabolite-driven, multi-tissue signalling system that links cold temperature to enhanced longevity and proteostasis in Caenorhabditis elegans. Cold temperature upregulates the biopterin-synthesis enzyme CAT-4 (GCH1 in humans), increasing production of dihydrobiopterin (BH2), a transportable reservoir for the bioactive...

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