Aging & Longevity

CONCLUSION: The co-occurrence of slow gait and mild cognitive impairment (MCI-SG) represents a distinct high-risk clinical phenotype strongly linked to AD pathology. Aβ and APOE ε4 show differential associations across the gait-cognitive spectrum. Integrated assessment of gait and cognition improves risk stratification in older adults and may guide early intervention strategies.

Underrepresented populations, often characterized by minority ethnicity, sex/gender or low socioeconomic status, have a higher risk burden and more adverse lifetime experiences of conditions negatively impacting cognitive health than better represented populations. There are several methodological challenges of research in and with marginalized populations that hinder research on improvements to their cognitive health. This review aims at presenting challenges of recruitment, data collection,...

The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation,...

Cardiac fibrosis, a major pathological hallmark of aging that leads to heart failure, is characterized by excessive collagen deposition. Our knowledge of what sustains collagen synthesis in the aging heart is still very preliminary. Here, we uncover a central role for chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, in this process. We demonstrate that CMA is suppressed in the aging heart, which promotes collagen overproduction in fibroblasts, whereas enhancing CMA...

Immune aging impairs T cell-mediated tumor control as well as cancer immunotherapy outcomes. The most important drivers of T cell dysfunction in aged tumors remain unknown. We performed single-cell CRISPR screens to identify Dusp5 and Zfp219 as key regulators of CD8^(+) T cell persistence and effector differentiation within aged tumors. Loss of Dusp5 increased extracellular signal-regulated kinase (ERK) phosphorylation and globally enhanced T cell proliferation. Conversely, Zfp219 deletion...

CONCLUSIONS: Age was the primary correlate of TL. Burnout, sleep-related impairment, and mental quality of life may moderate the association between FPG and TL. These exploratory findings suggest that addressing both psychological and cardiometabolic health may support TL in working adults.

Late-Onset Hypogonadism (LOH), also known as male menopause syndrome, is a common health problem plaguing middle-aged and elderly men. Its core pathophysiological change lies in the progressive decline of testosterone levels in men with age. This leads to a series of symptoms involving sexual function, physical, and psychological aspects, seriously affecting the quality of life and overall health of patients. The core pathophysiological link of LOH lies in the progressive decline of testosterone...

Myocardial ischemia-reperfusion injury (MIRI) in patients with acute myocardial infarction (AMI) after thrombolytic therapy or percutaneous coronary intervention is one of the diseases with threatening health and increasing mortality. Despite decades of research, the precise mechanisms of MIRI remain incompletely understood. Ageing is considered one of the factors that exacerbate MIRI. Emerging evidence highlights that protein post‑translational modifications (PTMs) serve as critical regulators...

Cellular senescence is a complex, highly regulated cell state induced by cellular damage and stress. Senescence is central to many areas of biology, with roles in tumour suppression, tissue regeneration, antiviral defence and diverse age-related pathologies. Senescence is characterized by stable cell cycle arrest, metabolic alterations, chromatin remodelling and the secretion of pro-inflammatory and tissue-modifying factors that are collectively termed the senescence-associated secretory...

Senescent cells promote tissue dysfunction in part through the senescence-associated secretory phenotype (SASP)¹. Cytosolic mitochondrial nucleic acids activate innate immune signalling to initiate this inflammatory programme^(2,3). Here we show that mitochondrial metabolism provides a second layer of control that enables execution of the inflammatory programme. In senescent cells, the mitochondrial pyruvate-citrate-acetyl-CoA axis is upregulated, increasing the availability of acetyl-CoA to...

Cellular senescence was initially defined in vitro as a stable cell-cycle arrest that occurs after repeated replication, but it is now recognized as a heterogeneous state shaped by cell type, species, senescence-inducing stress, tissue microenvironment and time. To organize this complexity, we propose the term 'senotype' to classify senescent cells by their inputs, molecular features and functional effects. We outline a practical framework incorporating: (1) cell identity and context; (2)...

Age-related changes in the immune system result in pronounced vulnerability to acute infections and cancers, and in dysregulated inflammation and wound healing that fuel many chronic diseases. Although we understand much about some of these changes, gaps in mechanistic knowledge remain, in part hindered by a lack of well-validated in vitro models of immune aging. We propose that multidisciplinary approaches, nucleated at the interface of immunology, gerontology and engineering, have the...

Statin optimization in older adults is increasingly relevant within the geroscience framework of cardiovascular ageing. This randomized controlled trial evaluated whether pharmacist-led pharmaceutical care improves lipid outcomes and statin adherence in community-dwelling older adults receiving primary care. A total of 99 patients aged 65 years or older on long-term statin therapy were randomized to usual care or structured pharmacist-led care delivered every 3 months. The primary outcome was...

Targeting biological processes of aging is a central goal of geroscience; however, limited data exist regarding the feasibility of incorporating biological aging biomarkers into dietary intervention trials. We conducted a pilot feasibility study among 34 adults aged 48-81 years with metabolic syndrome, a condition associated with elevated risk of age-related cardiometabolic disease and advanced biological aging. Participants consumed 1 oz of tree nuts and two tablespoons of extra virgin olive...

CONCLUSION: Systemic inflammation and metabolic dysregulation were associated with poorer cognitive performance, particularly executive dysfunction, in this rural aging cohort. These findings, while modest in effect size, support the importance of cardiometabolic health in cognitive aging, motivating future longitudinal and mechanistic studies.

CONCLUSION: The Adgrl2-Camk2d-TRPV1 signaling axis is a core driver pathway of perimenopausal cognitive impairment, exacerbating neuronal damage by mediating calcium overload, neuroinflammation, and metabolic disorders. This discovery provides a novel pathological mechanism for perimenopausal cognitive impairment, identifies Adgrl2 and TRPV1 as potential therapeutic targets, and designates Ca^(2+) as an ideal diagnostic biomarker, offering significant support for clinical diagnosis, treatment,...

In Hutchinson-Gilford progeria syndrome (HGPS), dysfunctional autophagy results in the accumulation of progerin, a lamin A mutant variant that alters a plethora of processes, inducing senescence and driving premature aging. Therefore, the elimination of progerin through autophagy restoration emerges as a therapeutic intervention against HGPS. However, a comprehensive study of autophagy flux in HGPS remains to be addressed. In this study, the dynamics of autophagy in HGPS fibroblasts were...

Sensory impairment (SI) and accelerated epigenetic aging are both linked to later-life vulnerability, yet their joint value for risk stratification remains poorly understood. We investigated whether the co-occurrence of sensory deficits and accelerated epigenetic aging identifies older adults at heightened risk of functional decline and mortality. We analyzed data from 2,395 participants in the 2016 wave of the Health and Retirement Study with valid DNA methylation (DNAm) and sensory data....

Fractures of long bones such as the femur are a common and serious health concern in the elderly, triggering immune responses essential for healing but also affecting remote organs like the liver. With age, the risk of fractures and immune imbalance increases, raising the likelihood of organ damage, infections, and mortality. To better understand age-dependent hepatic responses to bone injury, this study investigates early immune responses in the liver following femoral osteotomy, used here as a...

Epigenetic clocks are widely used to estimate biological age and predict health outcomes, but their translational value depends not only on accuracy but also on reliability. Using the TranslAGE platform, we evaluated both technical and biological reliability across 18 DNA methylation-based aging biomarkers, including chronological, mortality, and pace-of-aging clocks. Most clocks demonstrated excellent technical reproducibility across replicate assays on EPIC and 450 K arrays. However, several...