Every article, presentation, spotlight, and news item we've tagged to Hallmarks of Aging.
Showing 145–168 of 225
UNC45B, a myosin chaperone protein, declines with age and is required to maintain fast-twitch muscle force and mass. Loss of UNC45B in skeletal muscle triggers a cascade of systemic effects: reduced contractile capacity precedes atrophy, followed by bone fragility, lower body temperature, and sleep disruption.
A correction to a study examining how ad libitum feeding can extend lifespan through mechanisms opposite to caloric restriction, particularly involving energy-splicing pathways. This finding challenges the assumption that caloric restriction is the only dietary approach to lifespan extension and suggests multiple metabolic routes can achieve similar longevity outcomes.
Cellular reprogramming—the process of resetting aged cells to younger functional states through partial application of reprogramming factors—represents a fundamental shift in how aging is understood: not as irreversible damage accumulation, but as a modifiable biological state. Clinical trials are imminent, and the field has moved from theoretical elegance to therapeutic platform with potential applications across age-associated diseases.
Blocking the ghrelin receptor improves muscle endurance and mitochondrial function in aging mice without affecting muscle mass or lifespan. Both genetic deletion and pharmacological inhibition restore markers of mitochondrial renewal, suggesting this pathway is a viable therapeutic target for age-related muscle decline.
Aging impairs intestinal mitochondrial energy production, reducing HDL3 synthesis and disrupting the gut-liver axis, allowing inflammatory lipopolysaccharide to damage the liver. NMN restores NAD+ availability, rebuilds HDL3 production, and reverses this age-related hepatic injury in experimental models.
Cambrian Bio received $30.8 million in ARPA-H funding to test whether a selective mTORC1 inhibitor can preserve intrinsic capacity—the physical and metabolic resilience that maintains function during aging—before disease manifests. This represents a fundamental shift from treating established disease to intervening in the aging process itself, with success measured through a composite biomarker framework rather than disease endpoints.
SIRT6, a sirtuin protein, protects against neurodegenerative diseases by maintaining nucleolar function and constraining protein synthesis, preventing the accumulation of misfolded proteins that drives age-related brain pathology. This mechanism represents a direct intervention point in proteostasis failure, a primary driver of cognitive decline.
Centenarians maintain immune homeostasis through selective enhancement of cytotoxic immune cells (NK cells, CD8+ T cells, γδ T cells) paired with suppression of inflammatory pathways in adaptive immune populations. This remodeling of immune composition represents a compensatory adaptation mechanism that extends health span and informs potential interventions against immunosenescence.
Losartan, an angiotensin II receptor blocker, partially reversed aging-related metabolomic signatures in both aged mice and pre-frail older men, with effects dependent on functional angiotensin II receptors and correlating with improved survival in treated mice. The drug produced dose-dependent metabolic rejuvenation in humans and normalized age-related shifts in circulating metabolites, particularly lipids and amino acids.
Telomir-1 (Telomir-Zn) modulates intracellular metal balance by increasing zinc and reducing iron, influencing epigenetic regulation and cellular stability without triggering cytotoxic stress. This mechanism addresses oxidative stress and genomic integrity pathways implicated in aging and cancer biology.
SIRT6 maintains proteostasis by suppressing ribosomal gene expression and translation rates through nucleolar control. Without functional SIRT6, excessive protein synthesis overwhelms the folding machinery, leading to protein aggregation and accelerated neurodegeneration in aging models.
Natural killer cells from older adults show reduced capacity to eliminate senescent and cancer cells due to impaired granule release and cytotoxic machinery, not recognition defects. Targeting elevated Cdc42 protein and restoring microtubular organization represents a potential intervention to restore NK cell function with age.
Exercise triggers release of exosome-delivered eNAMPT, which activates hepatic SIRT1 and autophagy to reverse age-related fatty liver disease, inflammation, and fibrosis in aged mice. This mechanism establishes a biochemical pathway through which physical activity protects metabolic health during aging.
Allosteric Bioscience is using AI and quantum computing to model molecular mechanisms of aging, targeting pathways including Lamin A, tryptophan metabolism, DNA repair, and mitochondrial function. The approach aims to identify modulators that could reduce age-related disease and extend lifespan.
Aerobic exercise induces measurable transcriptome changes in aged skeletal muscle, activating pathways associated with mitochondrial function, protein synthesis, and cellular stress resilience. These molecular shifts provide a mechanistic explanation for how structured movement preserves muscle quality and metabolic capacity across the lifespan.
SLC25A51, a mitochondrial NAD transporter in fat cells, declines with age and directly regulates adipose tissue energy metabolism and systemic insulin sensitivity. Loss of this transporter accelerates metabolic disease phenotypes; its restoration protects against obesity and insulin resistance in aging.
Senescent cell immunogenicity varies substantially by cell type and the trigger that induced senescence. RAS-induced senescent myoblasts activated immune responses, while senescent fibroblasts, endothelial cells, and lung progenitors showed limited or no immunogenicity despite expressing senescence markers.
Muscle fiber disorganization, quantified as a homeostatic dysregulation index, independently predicts mobility decline and reduced mitochondrial function in adults over 70, regardless of muscle mass. This establishes structural entropy as a measurable mechanism of skeletal muscle aging separate from loss of size alone.
Telomerase (TERT) in myeloid cells prevents senescence and pro-inflammatory polarization through mechanisms independent of telomere length. Loss of myeloid TERT drives foam cell formation, dyslipidemia, pulmonary fibrosis, and cardiac dysfunction—establishing TERT as essential for preventing aging-associated multi-organ pathology.
Natural killer cells from older adults fail to clear senescent fibroblasts due to overactivation of the Cdc42 protein, which disrupts the cellular machinery required for releasing cytotoxic granules and producing ATP. Pharmacological inhibition of Cdc42 restores this clearing capacity and offers a potential therapeutic target for age-related disease driven by senescent cell accumulation.
Wearable devices tracking activity rhythms reveal that irregular movement patterns correlate with systemic inflammation and accelerated biological aging. This connection between circadian disruption and aging rate offers a quantifiable marker for longevity risk that precedes clinical disease.
BCL XL-PROTAC, a senolytic agent, selectively eliminates senescent cells in COPD airway tissue while promoting proliferation of healthy cells. This approach addresses a core driver of age-related lung disease and suggests a therapeutic pathway for restoring lung cell function in COPD patients.
Researchers encapsulated healthy mitochondria in red blood cell membranes to deliver them into diseased cells, achieving efficient uptake and functional restoration across multiple cellular models of mitochondrial dysfunction. This addresses a long-standing barrier in mitochondrial replacement therapy and demonstrates potential for treating mitochondrial diseases and age-related energy decline.
RNASEK, an enzyme that degrades circular RNA accumulation in cells, extends lifespan in model organisms by removing a form of molecular waste that accelerates aging. This identifies a specific degradation pathway central to cellular longevity.
