Aggregator

Mitochondrial dysfunction is increasingly recognized as a shared downstream pathogenic mechanism across a wide spectrum of neurological disorders, ranging from primary mitochondrial diseases to conditions including amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease, multiple sclerosis, hereditary ataxias and idiopathic inflammatory myopathies. This Review examines the role of mitochondrial biomarkers in improving diagnostic accuracy, patient stratification and monitoring of...

Lipodystrophies are a group of disorders featuring reduced adipose tissue mass or function, which often leads to significant metabolic disease, reduced lifespan and impaired quality of life. Individuals with congenital generalised lipodystrophy (CGL) have severely reduced adipose tissue mass. The loss of healthy systemic lipid storage typically causes hepatic steatosis and lipoatrophic diabetes. In addition, adipocyte-secreted hormones including leptin and adiponectin are dramatically reduced....

No abstract

Endothelial cells (ECs) are critical regulators of vascular function and exhibit tissue-specialized roles. During aging, these cells become dysfunctional, resulting in increased susceptibility to cardiovascular disease. Although single-cell transcriptomics has revealed extensive endothelial heterogeneity, a comprehensive atlas of human EC transcriptomes over the course of the adult human lifespan has been lacking. Here, we present the Human Aging Endothelial Cell Atlas (HAECA), a harmonized...

Neurodegenerative diseases are emerging as an important consequence of population ageing in sub-Saharan Africa (SSA), but their scientific relevance extends beyond a projected rise in case numbers. SSA combines exceptional human genomic diversity with marked heterogeneity in vascular and metabolic risk, infection, nutrition, occupational exposures, air pollution, and access to health care. This combination creates an underused setting in which to study why biological ageing produces...

Blood phosphorylated tau 217 (p-tau217) accurately detects Alzheimer's disease (AD) pathology but is also elevated in amyotrophic lateral sclerosis (ALS), likely reflecting peripheral (big) tau released from muscle. Assays selectively measuring brain-derived (BD-) tau and BD-p-tau217 are therefore needed. We analysed serum BD-tau and p-tau217 in ALS (n = 139), AD (n = 101) and controls (n = 75) using direct immunoassays and after BD-Tau immunoprecipitation (BD-Tau-IP), and tau species in brain...

No abstract

CONCLUSION: Bibliometric and semantic analyses indicate growing research interest in cell-type-specific senescence, inflammatory-fibrotic remodelling, HF phenotype heterogeneity, biomarkers, and senotherapeutics. These findings highlight opportunities for integrating mechanistic research with clinical investigation. Future studies should prioritize cell-specific senescence atlases, multidimensional biomarkers, comorbidity-aware HF stratification, and cautious evaluation of senotherapeutics in HF...

Global health policies and the World Health Organization consistently promote aging in place, reflecting the strong preference of older adults to remain in their home environments. Yet frailty, cognitive decline, caregiver exhaustion, and social vulnerability frequently make nursing home admission necessary and position institutional care as the default response to severe dependency. The COVID-19 pandemic exposed vulnerabilities of nursing home care and renewed debate about the sustainability of...

Corpus callosum microstructure is a proposed risk biomarker for vascular contributions to cognitive impairment. This study compared corpus callosum microstructure measures from the "Standard Model" biophysical diffusion model with diffusion tensor and kurtosis imaging (DTI, DKI) measures for differences related to age and cerebral small vessel disease (cSVD) in a population-based sample of cognitively unimpaired older adults (n = 112, mean age 69.9). Standard Model measures included axonal water...

Whether a decline in taurine drives aging is debated, and despite high millimolar intracellular concentrations, its function as a potential guardian of cytosolic homeostasis is unclear. Here, we show that aging increases circulating taurine concentrations in humans and mice. Further elevating taurine in aged mice enhances health span, engaging anti-inflammatory pathways previously linked to youthfulness, and reduces mortality from sepsis and inflammasome-mediated inflammation, suggesting an...

Physical activity promotes health primarily by decelerating the aging process. Bone is one of the tissues capable of sensing mechanical force and can adapt to different physical demands. However, its role in whole-body aging is unknown. We found that reduced mechano-sensing in osteocytes, caused by deletion of the mechanosensory channel, Piezo1, accelerated whole-body aging in mice. Dynamic tibial axial loading (DTAL) in mice at 20-24 months of age extended both healthspan and lifespan...

Neurodegenerative diseases are emerging as an important consequence of population ageing in sub-Saharan Africa (SSA), but their scientific relevance extends beyond a projected rise in case numbers. SSA combines exceptional human genomic diversity with marked heterogeneity in vascular and metabolic risk, infection, nutrition, occupational exposures, air pollution, and access to health care. This combination creates an underused setting in which to study why biological ageing produces...

CONCLUSIONS: The present findings may provide mechanistic insights into the development of nutritional strategies to attenuate age-associated anabolic resistance and improve skeletal muscle oxidative metabolic function.

CONCLUSION: The Fasting ENHANCE study protocol outlines the methodology for evaluating the effect of TRE on cognitive and metabolic health in older adults with SCD. Results will inform future nonpharmacological interventions aimed at attenuating cognitive decline.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a molecularly distinct, highly immunogenic gastric cancer subtype, yet the role of tertiary lymphoid structure (TLS) during therapy remains unclear. Using a large locally advanced EBVaGC cohort (144 samples), combined with spatial transcriptomics (11 samples) and a single-cell atlas (77 samples), we show that EBVaGC exhibits enhanced TLS formation compared with EBV-negative gastric cancer, with invasive-margin TLS (IM-TLS) predicting...

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...