Hallmarks of Aging Library
Every article, presentation, spotlight, and news item we've tagged to Hallmarks of Aging.
Showing 169–192 of 401
Spatiotemporal Transcriptomics Characterizes Immune Microenvironment During Mouse Liver Aging
Aged livers accumulate exhausted CD8+ T cells predominantly in the portal vein zone, where periportal hepatocytes upregulate LPIN1 to promote immune dysfunction. This spatial immune dysregulation correlates directly with liver disease progression and identifies a therapeutic target for age-related hepatic pathology.
Aging effects on emotionality, cognition and brain mononuclear cells in Sprague-Dawley rats of both sexes
Aging in rats produces sex-dependent changes in emotional regulation, cognitive function, and brain immune cell populations, with females showing greater cognitive decline and males exhibiting more pronounced emotional dysregulation. These findings suggest that neuroinflammation and immune cell dynamics contribute to cognitive and emotional aging, with implications for understanding sex-specific vulnerabilities in human neurodegenerative conditions.
Perp Deficiency Induces Defective Negative Selection and Autoimmune Arthritis in Aged Mice
PERP protein deficiency impairs thymic negative selection—the process by which autoreactive T cells are eliminated during development—leading to accumulation of self-reactive CD4+ T cells and autoimmune arthritis in aged mice. This identifies a molecular mechanism linking defective immune tolerance to age-related autoimmunity.
Metal Ion Imbalance Drives Age-Related Eye Disease
Dysregulation of metal ion homeostasis—particularly iron, copper, and zinc—drives age-related ocular pathology through oxidative stress and protein aggregation. Restoring metal ion balance emerges as a tractable intervention point for diseases including macular degeneration and cataracts.
Integrin‐Binding Matricellular Protein Fibulin‐5 Maintains Epidermal Stem Cell Heterogeneity During Skin Aging
Fibulin-5, an extracellular matrix protein that declines with age, maintains epidermal stem cell function by activating YAP signaling through integrin binding. Loss of fibulin-5 reproduces age-associated changes in skin stem cell populations, identifying a molecular mechanism linking extracellular environment degradation to cellular aging.
Altered Cytokine‐Induced STAT3 and STAT5 Activation of Peripheral T Follicular Helper Cells Contributes to Vaccine‐Non‐Responsiveness in Aging and HIV
Aging and HIV infection shift peripheral T follicular helper cell signaling from IL-21–STAT3 toward IL-2–STAT5 activation, impairing the immune response to influenza vaccination. This signaling imbalance represents a measurable immune mechanism underlying vaccine non-responsiveness in older adults and people with HIV.
Regulation of Lipid Dysmetabolism and Neuroinflammation Progression Linked With Alzheimer's Disease Through Modulation of Dgat2
Dgat2, an enzyme controlling triglyceride synthesis, emerges as a critical regulator linking amyloid pathology to lipid accumulation and neuroinflammation in Alzheimer's disease. Suppressing Dgat2 in animal models restores cognitive function, synaptic integrity, sleep quality, and circadian rhythms while reducing neuroinflammatory signaling, indicating a conserved therapeutic target across species.
Vitamin C Alleviates Aging in Cynomolgus Monkeys
Iron accumulation drives a coordinated aging process termed ferro-aging, characterized by oxidative damage and cellular senescence across tissues. Vitamin C administration reversed aging markers and restored functional capacity in aged cynomolgus monkeys, suggesting a tractable intervention point in iron-dependent aging pathways.
CD47 Platelets Suppress Aging Inflammation in Centenarians
Centenarians carry genetic and platelet-based mechanisms that suppress age-related inflammation through CD47 expression, which dampens monocyte activation. The LAV-BPIFB4 variant drives this protective effect, and recombinant administration of the protein replicates these benefits in non-carriers, establishing a translatable therapeutic target for inflammaging and cardiovascular disease.
Senescence consortium targets biomarker gap
The Senotherapeutics Biomarker Consortium addresses a critical gap in senescence measurement standards across academia, industry, and regulators. Standardized biomarkers are essential to advance clinical translation of senotherapeutic interventions, as current measurement heterogeneity impedes trial reproducibility and regulatory confidence.
Macrophage senescence drives pregnancy loss in advanced maternal age
Decidual macrophages in advanced maternal age pregnancies exhibit accelerated senescence driven by FOXO3 deficiency and elevated uterine IL-6, resulting in pro-inflammatory polarization and impaired immune function. Adoptive transfer of young macrophages rescues adverse pregnancy outcomes, establishing cellular senescence as a reversible mechanism underlying age-related pregnancy complications.
Vitamin C Alleviates Aging in Cynomolgus Monkeys
Iron accumulation drives a coordinated aging process called ferro-aging through oxidative damage and lipid peroxidation; vitamin C reverses these markers in primate models. This identifies iron metabolism and lipid oxidation as actionable targets in cellular senescence.
The Immune System Ages Differently in Men and Women
Research into age-related immune changes reveals sex-dependent trajectories, with females showing greater alterations in immune cell populations and autoimmune gene expression than males. This sex-specific immunosenescence pattern has direct implications for infection risk, cancer susceptibility, and chronic inflammatory disease across the lifespan.
Gut Bacteria Strain Reverses Age-Related Lung Fibrosis
A Lactobacillus strain (L9) found in centenarians reduces pulmonary fibrosis in aging mice by 30% through a metabolite-signaling pathway that suppresses collagen synthesis. The mechanism operates through the JNK signaling cascade and senescence-associated inflammatory cytokines, establishing a direct gut-to-lung biochemical axis relevant to fibrotic disease prevention.
Autophagy‐Independent Function of ATG‐18 Is Essential for Gonadal Longevity in Caenorhabditis elegans
ATG-18, a protein long associated with autophagy, extends lifespan through a mechanism independent of autophagy itself when the germline is removed. In the intestine, ATG-18 extends lifespan by interacting with PCK-2, an enzyme involved in glucose production, revealing a tissue-specific, non-autophagic pathway to longevity.
Extracellular matrix: new insights into its role in female reproductive aging and potential therapeutic strategies
The extracellular matrix—the structural scaffold surrounding reproductive tissues—undergoes progressive degradation during female reproductive aging, compromising ovarian function and fertility. Targeting matrix preservation and remodeling represents a mechanistic approach to extending reproductive lifespan and potentially supporting broader aging-related outcomes.
Role of Succinate Dehydrogenase in Age‐Related Th17 Inflammation
Succinate dehydrogenase (SDH), a mitochondrial enzyme, becomes overactive in aging T cells and drives an age-related shift toward Th17 inflammatory responses. Inhibiting SDH in older adults' T cells reduces proinflammatory cytokine production, while restoring succinate levels in younger T cells reproduces the inflammatory profile seen in aging.
Correction to “The Activation of cGAS‐STING Pathway Causes Abnormal Uterine Receptivity in Aged Mice”
A published correction addresses methodological clarifications in research examining how the cGAS-STING innate immune pathway dysregulates uterine receptivity during aging. The work connects age-related immune activation to reproductive decline in mice, with implications for understanding fertility loss across aging.
Multi‐Omics Analysis of Human Blood Cells Reveals Unique Features of Age‐Associated Type 2 CD8 Memory T Cells
Aging drives accumulation of a distinct CD8 T cell population lacking CXCR3 that exhibits Th2-skewed transcriptional and epigenetic programming. This shift correlates with increased risk for asthma, chronic liver disease, and type 2 diabetes, suggesting age-related immune dysregulation follows a predictable molecular trajectory.
Muscle Mitochondria Protect Male Cognition Via Glucose; Female Via Inflammation
Skeletal muscle mitochondrial oxidative capacity predicts cognitive decline over a decade, with markedly different pathways between sexes: glucose metabolism in men, hematologic-inflammatory signaling in women. This sex-differentiated mechanism reveals that identical biomarkers may reflect distinct physiological processes depending on biological sex.
Avoidance of rejuvenation: a stress test for evolutionary theories of aging
Evolutionary theory predicts that organisms should invest in rejuvenation when it is energetically favorable, yet most do not. This paradox reveals fundamental constraints on aging that challenge current models of senescence and suggests the biological capacity for rejuvenation may be far more limited than previously assumed.
Affecting a Signaling Pathway Alleviates Alzheimer’s in Mice
Somatostatin overexpression in neurons reduces microglial activation and inflammatory signaling while enhancing amyloid-β clearance in an Alzheimer's mouse model. Existing drugs targeting this pathway suggest translational potential for addressing neuroinflammation in cognitive decline.
Methylmalonic Acid, an Aging‐Associated Metabolite, Accelerates Intervertebral Disc Degeneration by Inducing Disc Vascularization via the CCL7/JAK2‐STAT3/VEGF Signaling Axis
Methylmalonic acid accumulates in aging intervertebral discs and drives degeneration through pathological vascularization via the CCL7/JAK2-STAT3/VEGF signaling pathway. VEGF receptor inhibition slowed disc degeneration in preclinical models, establishing vascularization as a therapeutic target in disc disease.
Affecting a Signaling Pathway Alleviates Alzheimer’s in Mice
Overexpression of somatostatin, a neuropeptide normally produced by neurons, reduces microglial activation and amyloid-β burden while improving cognitive function in an Alzheimer's disease mouse model. The finding identifies a previously untested communication pathway between neurons and immune cells that becomes dysregulated in the disease and offers a target for existing pharmaceuticals.