Every article, presentation, spotlight, and news item we've tagged to Hallmarks of Aging.
Showing 97–120 of 239
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 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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
T cells retain pro-inflammatory characteristics long after weight loss, perpetuating immune dysregulation in previously obese individuals. This 'obesity memory' may persist for years in humans despite normalization of body mass, suggesting that metabolic recovery and immune recovery operate on different timelines.
Exosomes in the gut lumen change composition with age, with those from older mice directly impairing barrier integrity and insulin sensitivity in younger recipients, while young exosomes reverse these effects in older mice. This identifies a specific molecular mechanism linking intestinal barrier dysfunction to metabolic aging.
Adults with arterial stiffness show a distinct immune remodeling pattern driven by CD4+ T cell dysfunction that differs from typical aging-related immune decline. This paradoxical expansion of dysfunctional T cell clones suggests a disease-specific immune pathway in early vascular aging, detectable through peripheral immune profiling before clinical cardiovascular manifestations appear.
Vascular injury triggers rapid nuclear deformation in arterial smooth muscle cells, accelerating cellular senescence through prelamin A accumulation. Zinc supplementation partially restores normal nuclear morphology by supporting the enzyme Zmpste24, which processes this senescence-driving protein.
Preclinical Parkinson's research has relied on young animal models and acute toxin paradigms that fail to capture the disease's age-dependent biology. The PD-AGE roadmap calls for aging-integrated models—using genetic systems with gradual phenotypes and crossing them with accelerated aging strains—to better reflect how Parkinson's actually develops in older humans and improve translational reliability.
Somatic mutations accumulating in microglia—brain immune cells—correlate with Alzheimer's disease pathology and cognitive decline. These acquired genetic variants, distinct from inherited risk factors, represent a previously underappreciated mechanism driving neurodegeneration and suggest new intervention points before symptomatic disease emerges.
Dendritic cell migration from the gut declines with age, impairing vaccine response. Oral delivery of yeast-derived nanoparticles restores this migration pathway and vaccine efficacy in aged mice, pointing to a specific mechanism by which immune function deteriorates and can be supported.
