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Lawmakers spend big on home state science projects
Kentucky Senator Mitch McConnell, king of congressional earmarks, steers $165 million to his alma maters
Associations of chinese-modified MIND diet with low muscle mass and physical performance among old adults in china: findings from the CLHLS 2018 national survey
CONCLUSION: Greater adherence to the cMIND dietary pattern is independently associated with lower probability of LMM and better physical performance among older Chinese adults. These findings suggest potential benefits of promoting MIND diet principles for maintaining musculoskeletal health in aging populations.
Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4
Tyrosine nitration alters the structure, function, and cellular localization of proteins and is implicated in the pathology of multiple diseases [G. Ferrer-Sueta et al., Chem. Rev. 118, 1338-1408 (2018), H. Ischiropoulos, Arch. Biochem. Biophys. 356, 1-11 (1998), I. Griswold-Prenner et al., J. Biol. Chem. 299, 105038-10554 (2023)]. Although protein nitration is assumed to proceed via nonspecific chemical mechanisms, it is highly selective, suggesting the possibility of enzymatic catalysis. Here,...
PTP1B inhibition promotes microglial phagocytosis in Alzheimer's disease models by enhancing SYK signaling
Amyloid β (Aβ) accumulation is a hallmark of Alzheimer's disease (AD). Emerging evidence suggests that impaired microglial Aβ phagocytosis is a key feature in AD, highlighting the therapeutic potential of enhancing this innate immune function. Here, we demonstrate that genetic deletion or pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) ameliorated memory deficits and reduced Aβ burden in APP/PS1 mice. Moreover, we show that PTP1B was highly expressed in microglia, and its...
Dopamine antagonists-induced parkinsonism: the crucial role of individual susceptibility associated to positive family history
No abstract
A common 19 bp APOE enhancer deletion is protective against Alzheimer's disease in African Americans
The APOE-ε4/ε4 genotype is the strongest genetic risk factor for sporadic Alzheimer's disease, though the relative risk is diminished in individuals with African ancestry. Through analysis of phased APOE alleles, we identify a 19 bp deletion approximately 1.1 kb distal to the APOE 3'UTR in a SPI1 microglial transcription factor binding site. The deletion is present in 60% of African American APOE-ε4 homozygotes and reduces Alzheimer's disease odds ratio relative to individuals without the...
Gut Microbiota-Derived Metabolites as Immune Modulators in Aging and Age-Related Chronic Inflammatory Diseases
Age-associated dysbiosis, marked by shifts in the composition of gut microbiota and gut microbiota-derived metabolites (GMDMs), is increasingly implicated in driving systemic low-grade inflammation during aging. The disrupted GMDM pools, including altered levels of short-chain fatty acids (SCFAs), secondary bile acids (BAs) and tryptophan (Trp) metabolites, lead to mucosal barrier dysfunction, immunometabolic dysregulation, and modulation of innate and adaptive immune cells. In turn, this...
Aging and Neuropathic Pain: Mitochondria-to-Glia Cascade, Systems Mechanisms, and Therapeutic Strategies
Neuropathic pain (NP) creates a severe condition that primarily affects elderly people because their accumulated neurobiological changes make them more susceptible to persistent pain. The aging process leads to multiple mechanisms that combine neurodegeneration with immunosenescence and mitochondrial dysfunction and impaired autophagy and glial priming and ion channel dysregulation to create a harmful nociceptive environment. This review examines how mitochondrial breakdown and dysfunctional...
Blood Flow and Angiogenesis; Major Mechanisms Mediating Healthful Longevity
While human lifespan has increased dramatically over the past century, the extension of healthspan, the period free of chronic age-related disease, has lagged behind. Blood flow and angiogenesis are significantly reduced in aging humans, playing a crucial role in mediating cardiovascular disease and heart failure - major causes of reduced lifespan. However, these mechanisms have not been studied as extensively as cellular and molecular mechanisms in animal models. Healthful aging, due to...
Uncovering treatment effect heterogeneity in pragmatic gerontology trials
Detecting heterogeneity in treatment response enriches the interpretation of gerontologic trials. In aging research, estimating the intervention's effect on clinically meaningful outcomes poses analytical challenges when outcomes are truncated by death. For example, in the Whole Systems Demonstrator trial, a large cluster-randomized study evaluating telecare among older adults, the overall effect of the intervention on quality of life was found to be null. However, this marginal intervention...
External Validation of SCORE2-OP for Predicting Cardiovascular Mortality in Frail Geriatric Outpatients
CONCLUSIONS AND IMPLICATIONS: In a frail older outpatient population, SCORE2-OP showed notable discrimination for CVD mortality in those without ASCVD history. This suggests that SCORE2-OP can be used for CVD risk estimation in these frail outpatients.
p16-mediated G0/G1 cell cycle arrest leads to SASP and fibrosis in Fuchs endothelial corneal dystrophy
Fuchs endothelial corneal dystrophy (FECD) is an age-related disorder characterized by excessive extracellular matrix (ECM) deposition and loss of corneal endothelial cells (CEnCs), eventually leading to corneal blindness. Despite known environmental and genetic contributors, the roles of aging and hormonal influences, particularly in the predominantly female population, remain underexplored in FECD. This study investigates the impact of chronic exposure to combined ultra-violet (UV-A) light and...
Delivery of peptide coacervates to form stable interaction hubs in cells
Cells contain membrane-bound and membraneless organelles that operate as spatially distinct biochemical niches. However, these reaction centers lose fidelity due to aging or diseases. A grand challenge for biomedicine is restoring or augmenting cellular functionalities. An excited strategy is the delivery of protein-based materials that can directly interact with cellular biological networks. In this study, we sought to develop long-lasting materials capable of cellular uptake, akin to...
Probiotic Lactiplantibacillus plantarum OL3246 supports healthy aging by enhancing quality of life, reducing inflammation, and modulating gut microbiota: a pilot study
Aging is accompanied by low-grade intestinal inflammation, shifts in gut microbiota, and impaired oxidative balance. Probiotic supplementation has been proposed to mitigate these processes, yet evidence in elderly populations remains limited. In this pilot trial, older adults received oral Lactiplantibacillus plantarum OL3246 or placebo, with assessments including fecal calprotectin and zonulin as markers of intestinal inflammation, systemic oxidative stress parameters, self-reported quality of...
ER remodelling is a feature of ageing and depends on ER-phagy
The endoplasmic reticulum (ER) comprises an array of subdomains, each defined by a characteristic structure and function. Although altered ER processes are linked to age-onset pathogenesis, it is unclear whether shifts in ER structure or dynamics underlie these functional changes. Here we establish ER structural and functional remodelling as a conserved feature of ageing across yeast, Caenorhabditis elegans and mammals. Focusing on C. elegans as the exemplar of metazoan ageing, we reveal...
ER gets out of shape with ageing
No abstract
Endothelial ZBTB16 preserves vascular health and cardiac function during aging
No abstract
Polarity-dependent modulation of sleep oscillations and cortical excitability in aging
CONCLUSION: In summary, anodal, but not cathodal, so-tDCS effectively enhanced thalamocortical interactions underlying memory consolidation. Furthermore, these findings highlight the importance of individual factors such as chronotype in brain stimulation responsiveness.
Early and progressive retinal microglial changes in APP<sup>NL-F/NL-F</sup> mouse model of Alzheimer's disease revealed by an automated image analysis software
Alzheimer's disease (AD) is characterized by the accumulation of misfolded proteins that trigger neuroinflammation and neuronal loss. The retina, as an extension of the central nervous system, mirrors these pathological processes and represents a potential biomarker. Microglial activation, a key component of neuroinflammation, can be morphologically assessed through automated image analysis. This study performed a quantitative and morphological analysis of retinal microglia in the...
Cellular Senescence in the Ascending Aorta and Complexity of Coronary Atherosclerosis
CONCLUSION: Increased expression of p16 and p21 in ascending aortic tissue is significantly associated with higher coronary atherosclerosis complexity in patients undergoing CABG. Among these biomarkers, p16 serves as an independent predictor of complex CAD, highlighting its potential role in vascular aging and atherosclerosis progression.