Aging & Longevity

Autosomal dominant mutations in TARDBP, encoding TAR DNA-binding protein 43 (TDP-43), cause amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is a hallmark of multiple aging-associated neurodegenerative diseases. Despite its pathological role, effective therapies remain limited by the lack of safe, potent molecules targeting TDP-43 neurotoxicity. Here we show that the conserved α-helical region spanning residues 320-340 (conserved region or CR) is a therapeutically actionable target for...

Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipidomics and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of submaximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy...

The review summarizes the context-dependent role of enhancer of zeste homolog 2 (EZH2) in cellular senescence and aging-associated tissue dysfunction. It discusses a conceptual shift from strong pharmacological EZH2 inhibition toward a more nuanced, context-dependent epigenetic modulation by natural compounds. Aging is associated with tissue‑specific alterations in EZH2 expression-both its decline and overexpression have been linked to cellular senescence, impaired regeneration, and age‑related...

Idiopathic pulmonary fibrosis (IPF) is a paradigmatic aging-related lung disorder. In this retrospective cohort study, we evaluated 101 treatment-naïve patients at diagnosis (T0) and a subgroup (n = 31) after one year of antifibrotic therapy (T1). Analyses included leukocyte telomere length (LTL), DNA methylation age [DNAmAge assessed by Horvath, Levine (PhenoAge), Skin & Blood, Hannum, BLUP, Elastic Net (EN), and a 5-CpG panel], age acceleration (AgeAcc), and genetic susceptibility. At T1, LTL...

Aging profoundly remodels the immune system, impairing defense, repair and homeostatic function across tissues. Because the immune system operates in every organ, its deterioration has been proposed to drive or exacerbate systemic dysfunction and accelerate overall biological aging, making it an attractive biomarker and target for geroscience-guided trials. Despite this central role, there is no consensus on how to quantify immune aging, especially in clinical trials. Here, we establish a...

Liver aging is characterized by chronic inflammation and metabolic dysfunction that drive progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Necroptosis, a pro-inflammatory form of cell death via the Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1)-RIPK3-Mixed Lineage kinase domain Like pseudokinase (MLKL) pathway, is activated in aging livers, and systemic inhibition of this pathway reduces hepatic inflammation and pathology. The cell type-specific...

CONCLUSIONS: This study revealed that nutritional status is independently associated with quality of life in older adults, independent of strong psychosocial determinants. Although depression, frailty, and loneliness were dominant predictors, the independent contribution of nutritional status suggests that nutritional assessment and interventions could be considered as an integral part of geriatric care. The findings highlight the potential role of comprehensive care models that combine...

CONCLUSIONS: Mutual aid among older residents was neither uniform across districts nor fixed over time. Rather, it was shaped by district-specific relational infrastructures and reconfigured through age-related changes in health, mobility, and everyday routines. Community interventions should therefore be tailored to the relational infrastructure already present in each district and should support modest, repeatable opportunities for reciprocal contact and gentle monitoring.

CONCLUSION: The present study highlights the substantial burden of malnutrition among older individuals. Two-thirds of the individuals were either at risk of developing malnutrition or had already developed malnutrition. As none of the sociodemographic factors were found to be associated, qualitative studies are needed to explore the various other reasons for developing malnutrition.

ObjectivesSocial security benefits are associated with better psychological health among older adults in resource-limited settings, yet the mechanisms underlying this association remain underexplored. We examined the role of healthcare accessibility in the relation between social security benefits and psychological health among older adults in Tanzania.MethodsWe analyzed cross-sectional data from a 2024 survey of Tanzanian adults aged 60 and above (n = 2,012) in four geographic zones. We...

All animals age. However, aging is a heterogeneous process, and individual organisms age differently. Moreover, within the same organism, cells or organs do not age at the same speed. For instance, neurodegeneration, a hallmark of aging, generally manifests later than other peripheral aging signs. The genetic determinants of aging are not completely understood. Gain-of-function (GoF) mutations in leucine-rich repeat kinase 2 (LRRK2^(GoF)) are major genetic risk factors for Parkinson's disease...

The RAD18 (E3) ubiquitin ligase, a key DNA damage tolerance regulator that also functions in DNA double-strand break repair, is overexpressed in the brain cancer glioblastoma. Here, we show that RAD18 promotes glioblastoma cell proliferation in the absence of exogenous damage, independently of its catalytic activity. RAD18 downregulation arrests glioblastoma cells in the G1 phase of the cell cycle, leading to senescence onset, with no apparent increase in DNA damage. We also show that RAD18...

Innate immune memory (trained immunity) is mediated by epigenetic and metabolic reprogramming of innate immune cells and hematopoietic progenitors, enabling altered responses to subsequent challenges. Mechanistically conserved across eukaryotes, trained immunity in mammals operates as a dynamically regulated, life-phase-specific system. The demands and constraints on innate immune memory shift across the life span: from tolerogenic programming and maternal immune transfer in fetal and neonatal...

Postovulatory oocyte aging (POA) is a key factor contributing to the decline in female fertility and the success rate of assisted reproductive technology. Currently, most studies on POA have focused on downstream phenotypes such as mitochondrial dysfunction and oxidative stress, while little is known about its key upstream regulatory factors. Here, we show that the downregulation of transcription factor Early Growth Response 1 (EGR1) is a key upstream event driving porcine oocyte aging....

CONCLUSIONS: Our study offers a new understanding of how the community environment may influence older people's support behaviors. Findings suggest that social cohesion and social belonging play distinct roles in relation to support provision among older people. Practices aimed at facilitating mutual support and well-being may need to take specific roles of different dimensions of community environment into account.

The intestine is one of the first organs to show signs of aging, including cellular changes, microbiota shifts, and reduced regenerative capacity. The different components of the gut-such as the epithelium (which is directly exposed to a diverse array of host-microbe interactions), the microbiota itself, and the underlying enteric nervous system-likely contribute to aging in distinct ways. Understanding their individual and interactive roles is key to elucidating the mechanisms of intestinal...

CONCLUSIONS: Heterogeneity among the homebound older adult population shapes care needs that in turn influence utilization patterns. Understanding these dynamics is crucial to targeting interventions like home-based primary care to the highest risk groups while tailoring care to individual needs.

[This corrects the article DOI: 10.3389/fnagi.2024.1476909.].

Sexuality in older age remains a taboo subject. Little is known about the perceptions and experiences of healthcare professionals when addressing this topic with older adults. This systematic review, registered in PROSPERO, aims to understand the perceptions, practices, and recommendations of healthcare professionals in primary and hospital care regarding the approach to sexuality and sexual health in older people. The 17 selected studies, conducted in six countries, show that physicians and...

A paradoxical inverse correlation between cancer and Alzheimer’s disease has been repeatedly observed in epidemiological studies. While cancer and Alzheimer’s disease share common risk factors, most notably aging, the risk of Alzheimer’s disease in patients with cancer is significantly reduced, and the risk of cancer in patients with Alzheimer’s disease is halved. The convergence of two distinct disciplines, cancer and Alzheimer’s disease, offers an exciting and untapped opportunity to generate...