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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

2 weeks 4 days 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

The TyrRS cascade: circadian gating of neuronal DNA repair and its collapse in aging

2 weeks 4 days ago
Age-related neurodegenerative diseases are characterized by progressive DNA damage in post-mitotic neurons against a backdrop of deteriorating circadian rhythms, yet the molecular link between these conjoined features of brain aging remains unclear. We propose the TyrRS cascade as that link: a signaling architecture in which the noncanonical nuclear functions of tyrosyl-tRNA synthetase (TyrRS/YARS1) schedule neuronal genome maintenance across the day through three coregulated streams,...
Sajish Mathew