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Children at risk for depression get “stuck” on sad faces
Depression may change which emotional faces children notice most, but the pattern appears to depend on family history. Children at higher familial risk became increasingly focused on sad faces, while lower-risk children with rising symptoms paid less attention to happy ones.
Brain scans reveal which disorders are linked to faster brain aging
A massive MRI study found that Alzheimer’s disease, mild cognitive impairment, psychiatric disorders, and addiction are associated with distinct patterns of accelerated brain aging. The strongest effects appeared in Alzheimer’s and mild cognitive impairment, while ADHD and autism showed no significant overall difference.
Lysosomal dysfunction in neurodegenerative disease
Examination of genetic risk factors associated with neurodegenerative diseases has provided important mechanistic insights into the pathophysiology of these disorders, and it has implicated defects in lysosomal function as a key component of the neurodegenerative process. The lysosome has a primary role in mediating degradation of both intracellular contents and endocytosed material from the extracellular space. Aggregation of misfolded proteins is a pathological mechanism that is observed...
Injury-transduced oligodendrocytes modulate neuroinflammation and glial activation in diseased and non-diseased central nervous system
Oligodendrocytes (OLs) are brain cells that make myelin, the insulating sheath that supports nerve signal transmission. Although oligodendrocyte dysfunction is common in the central nervous system (CNS), how these cells respond to injury remains incompletely understood. Here we show, using mouse models and mouse tissue analyses, that OLs respond to demyelinating diseases by increasing the expression and secretion of serine protease inhibitor clade A member 3N (SERPINA3N). This transition of...
Sustained algal-bacterial interactions promote accumulation of recalcitrant particulate carbon with accelerated radiocarbon aging signatures
Algal-bacterial interactions regulate the production and fate of marine particulate organic carbon (POC), yet their capacity to generate long-lived carbon sinks remains unclear. Using a two-year, nutrient-self-sustaining co-culture of Synechococcus and its mutualistic microbiota, we demonstrate that sustained algal-bacterial interactions promote the progressive accumulation of recalcitrant POC. Continuous release of algal-derived organic substrates, coupled with repeated microbial enzymatic...
Pulsed electromagnetic fields activate a peripheral interoceptive pathway to suppress sympathetic Npy for osteogenesis
Chronic stress-induced osteoporosis is a prevalent yet therapeutically challenging condition, with sympathetic overactivation as a key contributor. The dominant pathological mediator and strategies for its precise, non-invasive modulation remain unclear. Here, we identify sympathetic neuropeptide Y as a critical driver of this pathology. Using an unpredictable chronic mild stress model in male mice, we show that neuropeptide Y directly induces cellular senescence in bone marrow adipocytes,...
Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor gamma
Aging paradoxically leads to both a decline in skeletal muscle mitochondrial function and a shift in muscle composition that favors fibers rich in mitochondria. Yet the biological rationale and mechanism underlying this phenomenon remain largely unknown. Here we show that synthesis of the mitochondrial membrane lipid, cardiolipin, causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle. By mimicking the aging decline of skeletal muscle...
Exercise enhances aged chondrocyte health through microRNA-29-enriched extracellular vesicles
Extracellular vesicles (EVs) have been proposed to be mediators of the health-promoting effects of exercise throughout the body, but how EVs communicate these beneficial signals to recipient cells remains unknown. Here we interrogated these mechanisms using articular cartilage as a model. Network propagation of EV microRNA perturbations on a cartilage-specific network identified microRNA-29 as an exercise-responsive regulator of cellular aging. Consistent with this prediction, a 3-month aerobic...
Author Correction: Destabilizing heterochromatin by APOE mediates senescence
No abstract
Sex- and age-specific patterns in bone, muscle, and fat across adulthood and their relation to osteosarcopenic adiposity phenotype: a cross-sectional study
Evidence suggests that age-associated differences in body composition-bone/muscle/adipose tissue-are nonlinear, but their timing, sex-specific features, and relation to osteosarcopenic adiposity (OSA) phenotype remain poorly defined. OSA is characterized by the coexistence of osteopenia/osteoporosis, sarcopenia, and excess or redistributed adiposity. We examined sex- and age-specific patterns and inflection points for bone, muscle, fat, and intramuscular adipose tissue (IMAT) in cross-sectional...
Cervical lymphadenectomy impairs brain lymphatic clearance and synaptic proteostasis
Meningeal lymphatic vessels drain brain fluid and waste into the cervical lymph nodes, but how removing these nodes during surgery affects brain health is unknown. Retrospective analysis of cancer patients who underwent neck lymphadenectomy without chemo-radiation therapy found that up to 25% developed mild-to-severe cognitive impairment, and neuroimaging showed accelerated temporal horn enlargement after bilateral surgery. To determine mechanistically how cervical lymphadenectomy contributes to...
Microglia with distinct origins and non-canonical phenotypes coexist within the border-like niche of the brain's circumventricular organs
Circumventricular organs (CVOs) are small brain regions lacking a blood-brain barrier, giving neurons direct access to blood-borne signals, yet how these microenvironments shape the origin and phenotype of local macrophages remains unclear. Using multi-omics, we characterized the immune landscape of two CVOs, the area postrema (AP) and median eminence (ME), revealing brain-border-like environments with a unique macrophage compartment. CVO microglia showed a distinct, heterogeneous phenotype,...
Direct Pharmacological Activation of AMPK Extends Lifespan in Yeast, Worms and Flies
AMP-activated protein kinase (AMPK) is a key evolutionarily conserved sensor of energy homeostasis and plays a central role in metabolic health and disease. AMPK has also been implicated in ageing; however, most in vivo drug studies rely on the use of indirect activators, such as metformin, which have complex modes-of-action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in...
Autologous cytokine-induced NK cells as candidate cellular senolytics: evidence, obstacles, and the experiments still needed
Cellular senescence and chronic low-grade inflammation occupy a central, mechanistically coupled position among the hallmarks of aging. Natural killer (NK) cells decline in per-cell cytotoxicity with age, and lower NK cell cytotoxicity has been associated with higher cancer incidence and infection-related mortality in older adults. NK cells are also endogenous effectors of senescent-cell clearance, engaging stress-induced NKG2D and DNAM-1 ligands and depending on perforin-mediated cytolysis....
Reproducible cortical links between functional hierarchy, structure, and metabolism
Large-scale functional connectivity gradients provide a compact description of cortical organization, capturing hierarchical transitions from unimodal sensory systems to transmodal association cortex. Although these gradients have become a central framework for studying macroscale brain organization, it remains unclear whether they systematically map onto regional cortical biology. Here we show that functional gradient position robustly predicts cortical thickness and regional glucose...
Tau-induced increase in promoter-proximal RNA polymerase II pausing is linked to suppressed expression of long neuronal genes in a <em>Drosophila</em> tauopathy model
Tauopathies, including Alzheimer's disease, are age-related neurodegenerative disorders characterized by abnormal phosphorylation and buildup of microtubule-associated protein tau. Gene expression dysregulation is a key molecular feature of tauopathies, but how aging and disease interact to disrupt crucial transcriptional regulators and pathways remains largely unknown. Here, we examined how pathological tau affects gene expression programs in age-related neurodegenerative disease using a...
Prevalence and Risk Factors of Pain Among Older People in Mexico: Evidence From MHAS 2018
CONCLUSION: The prevalence of pain is relatively high among older people in Mexico. Targeted intervention measures should be taken to improve awareness of the risk factors and the prevention of pain.
Dietary CoQ10 Ameliorates Age-Related Megakaryocyte Dysfunction via COPS3-Mediated Activation of Autophagy
Age-related megakaryocyte (MK) dysfunction disrupts platelet production and may increase thrombotic risk, but whether coenzyme Q10 (CoQ10) restores MK homeostasis through autophagy remains unclear. Male C57BL/6J mice aged 1, 9, 15, 19, 21, or 23 months received CoQ10 for 12 weeks. Bone marrow MK proliferation, CD41/CD61 expression, DNA polyploidy, autophagy-associated proteins, and platelet phenotypes were evaluated. H(2)O(2)-induced senescent MEG-01 cells were used for pharmacological...
IGF-1/SLC25A33 Maintains Blood-Labyrinth Barrier Integrity by Suppressing TGF-β/Smad2-Mediated Pericyte Activation in Age-Related Hearing Loss
Age-related hearing loss (ARHL) is a prevalent sensory disorder in the elderly, yet the molecular mechanisms underlying cochlear aging remain incompletely understood. While insulin-like growth factor 1 (IGF-1) has been implicated in ARHL, its role in the stria vascularis, particularly in pericyte-mediated blood-labyrinth barrier (BLB) regulation, is poorly defined. We performed transcriptomic analysis of FACS-purified pericytes from young and aged mouse stria vascularis. Functional studies were...
α-Synuclein Promotes Atherosclerosis by Impairing Macrophage Autophagic Flux
Atherosclerosis, recognized as a prototypical age-associated vascular disease, is driven by macrophage foam cell formation. Individuals with Parkinson's disease (PD) exhibit an elevated risk for stroke. While α-synuclein (α-Syn) is known for its neuronal role in PD, its presence in the circulation and potential vascular effects remain unexplored. Here, we identify α-Syn as a previously unrecognized circulating factor that promotes atherosclerosis. α-Syn was detected in human atherosclerotic...