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Life Course Neighborhood Socioeconomic Disadvantage and Chronic Disease Accumulation in Mid- to Late Adulthood

39 minutes 55 seconds ago
ObjectiveThis study examines associations between neighborhood socioeconomic disadvantage during adolescence and early adulthood and chronic disease accumulation in mid- to late life.MethodsUsing Panel Study of Income Dynamics data linked to U.S. Census and American Community Survey data, we identify four trajectories of neighborhood disadvantage, namely persistent disadvantage, increasing disadvantage, decreasing disadvantage, and persistent advantage, and estimate their associations with...
Ying Huang

New mesothelioma drug turns cancer’s own defenses against it

5 hours 28 minutes ago
Scientists are testing a counterintuitive way to fight mesothelioma, an aggressive asbestos-linked cancer with few effective treatments. A new experimental mesothelioma drug kills cancer cells by disabling PRX3, an antioxidant defense that tumors use to survive intense oxidative stress. In an early clinical trial, it controlled disease progression in 67% of patients and produced encouraging survival results, raising hopes that the strategy could eventually be used against other cancers.

Scientists find an immune “false alarm” that may drive rapid aging

20 hours 34 minutes ago
Scientists have discovered that some severe genetic disorders linked to rapid aging may be driven not just by damaged DNA, but by the body’s overreaction to that damage. When broken DNA fragments leak into the wrong part of a cell, an immune sensor called cGAS can mistake them for signs of a viral infection, triggering chronic inflammation and even interfering with DNA repair itself.

Associations of physical fitness with brain structure, pathology and cognition in cognitively normal older adults

1 day ago
The role of physical fitness in cognitive reserve and brain maintenance remains unclear. We investigated the associations of muscular and aerobic fitness (VO(2)max) with markers of brain health and cognition in 353 cognitively unimpaired older adults (mean age = 72.77 ± 7.95 years; 177 females). Muscular fitness comprised handgrip strength, appendicular skeletal muscle mass, and Timed-Up-and-Go performance. Blood biomarkers of Alzheimer's pathology (Aβ(1-42)/Aβ(1-40), p-tau(217), GFAP) and...
Svenja Schwarck

APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics

1 day ago
Lipid droplets are dynamic cellular organelles that store neutral lipids and coordinate metabolic and stress-response pathways. In the brain, lipid droplets in glial cells, including astrocytes, have been implicated in Alzheimer's disease, but how genetic risk factors influence their composition and turnover remains poorly understood. APOE is the strongest genetic modulator of late-onset Alzheimer's disease and exists in common variants that confer decreased, neutral, or increased risk. Here we...
Carla Cuní-López

Sex-specific biological aging clocks across organs and omics

1 day ago
Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer's disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex invariance.Here we developed 38 sex-specific biological aging clocks across 15 organ systems. We first demonstrate the importance of sex-stratified training for constructing sex-specific healthy normative references and...
MULTI Consortium

HMGA1-HP1beta axis regulates premature aging in Hutchinson-Gilford progeria syndrome through chromatin remodeling

1 day ago
Hutchinson‑Gilford progeria syndrome (HGPS) is a rare premature aging disorder caused by mutations in the LMNA gene. High mobility group A1 (HMGA1) exhibits differential expression patterns across aging models. However, its roles and mechanisms in aging remain unclear. Here, we show a positive correlation between HMGA1 and the heterochromatin protein HP1β in multiple tissues of Lmna^(G609G/G609G), a classic genetic mouse model of HGPS to recapitulate typical premature aging features, and...
Qianying Hu

Cell senescence emerges as a hallmark and therapeutic target of chronic intracellular infection

1 day ago
Intracellular pathogens are ideal candidates for modelling the pathophysiology of chronic infection, as they hide within host cells and avoid immune clearance by reshaping cellular fate. This study unveils how the intracellular pathogen Mycobacterium abscessus (Mab) reprograms alveolar macrophages towards a senescent state -a multifaced phenotype marked by proliferative arrest, distinctive morphological shifts, activation of DNA damage signalling cascade, and secretion of senescence-associated...
E Scarpa

CK2alpha restriction of STING accumulation underlies systemic aging

1 day ago
Chronic activation of the cGAS-STING pathway drives inflammaging and cellular senescence. Although nuclear envelope (NE) barrier failure leading to cytoplasmic chromatin leakage is a key trigger, the molecular mechanisms governing STING activity at the NE during aging remain poorly understood. Here, we identify lamin A/C (LMNA) as a critical NE scaffold that orchestrates STING regulation by recruiting both STING and Casein Kinase 2 (CK2α). We demonstrate that LMNA facilitates the phosphorylation...
Jie Zhang

Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence

1 day ago
Cellular senescence is a state of irreversible cell cycle arrest triggered by telomere erosion, persistent DNA damage or chronic stress. The accumulation of senescent cells disrupts tissue function and contributes to aging and disease. Here, we employ mass spectrometry-based proteomics to systematically interrogate dynamic proteome changes at multiple levels during the progression of replicative cellular senescence. We demonstrate that proteome changes during senescence occur in a coordinated...
Nádia Da Silva Fernandes

Sex-specific biological aging clocks across organs and omics

1 day ago
Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer's disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex invariance.Here we developed 38 sex-specific biological aging clocks across 15 organ systems. We first demonstrate the importance of sex-stratified training for constructing sex-specific healthy normative references and...
MULTI Consortium