Metabolic Pathways Library
Every article, presentation, spotlight, and news item we've tagged to Metabolic Pathways.
Showing 73–96 of 148
Hypoxia-induced autophagic degradation of HIF-1α attenuates cellular aging and extends mammalian lifespan
Intervertebral discs age slowly due to selective autophagy of HIF-1α under naturally hypoxic conditions. A small molecule designed to replicate this mechanism across tissues may extend mammalian lifespan by modulating how cells respond to low-oxygen environments.
L-Nutra named Innovator Partner for the Longevity Show 2026
L-Nutra's fasting-mimicking technology platform, validated across 47 clinical trials and 18 university research centers, repositions precision nutrition as essential healthcare infrastructure rather than lifestyle optimization. The company's approach uses targeted nutrient formulations to trigger cellular repair mechanisms—autophagy and metabolic signaling—without the physiological stress of extended fasting, addressing metabolic dysfunction and age-related chronic disease at a systems level.
Three drugs in major study to prove their capacity to slow aging
UT Health San Antonio is launching VITAL-H, a $38 million clinical trial enrolling over 700 adults to test whether three existing drugs—rapamycin, semaglutide, and dapagliflozin—can slow biological aging in humans. This represents the first large-scale human trial specifically designed to evaluate pharmaceutical intervention in aging processes.
Elevated trimethylamine levels characterize impaired muscle mass response to leucine-enriched protein supplementation in older adults at risk of sarcopenia
Elevated trimethylamine—a gut-derived metabolite—predicts which older adults will fail to gain muscle mass from leucine-enriched protein supplementation. This biomarker distinction reveals that sarcopenia interventions require individual metabolic assessment, not one-size-fits-all protocols.
Pck1 Deficiency Drives Mitochondrial Dysfunction and Cellular Senescence in Adipocytes
Pck1 deficiency in adipocytes impairs mitochondrial function, causing fumarate accumulation that triggers oxidative stress, mtDNA release, and chronic inflammation—a mechanism linking metabolic dysfunction to aging. This identifies a targetable pathway in the progression of age-related metabolic disease.
MLKL-Driven Mitochondrial Stress Amplifies Senescence in Aging Liver
Hepatocyte MLKL accumulation in aging livers drives mitochondrial dysfunction and cellular senescence independent of necroptosis, amplifying inflammatory signaling across liver tissue through paracrine mechanisms. This identifies MLKL as a direct molecular driver of liver aging with potential therapeutic relevance to metabolic liver disease progression.
New findings link autophagy failure to early Alzheimer’s pathology
Impaired neuronal autophagy precedes amyloid-beta and tau pathology in Alzheimer's disease, suggesting that restoring cellular clearance mechanisms may address disease onset at a mechanistic level upstream of classical biomarkers. This positions autophagy dysfunction as a tractable target for intervention before irreversible neurodegeneration.
Ammonia Dysregulation: Liver Aging's Systemic Cascade
Hepatic ammonia metabolism declines with age through mitochondrial dysfunction and disrupted metabolic regulation, compromising the liver's capacity to maintain nitrogen homeostasis and triggering inflammatory and fibrogenic remodeling. This pathway represents a mechanistic link between liver aging and systemic dysfunction across multiple organ systems.
NR Supplements Reduce Muscle Epigenetic Aging; HIIT Shows Mixed Results
Nicotinamide riboside supplementation reduced epigenetic age acceleration in skeletal muscle over five months, while high-intensity interval training produced divergent effects depending on the measurement method used. Changes in mitochondrial content correlated with epigenetic aging shifts, suggesting mitochondrial function as a mechanistic link between these interventions and cellular aging markers.
Endothelial Sirtuins and Mitochondrial Function Are Associated With Testosterone Status: Implications for Accelerated Vascular Aging in Middle‐Age and Older Men With Low Testosterone
Middle-aged and older men with low testosterone demonstrate reduced mitochondrial respiration and decreased SIRT3 expression in vascular endothelial cells, indicating accelerated vascular aging through impaired oxidative stress regulation. This mechanism links testosterone deficiency directly to cardiovascular disease risk through mitochondrial dysfunction.
Adipose RNA Control Preserves Metabolic Flexibility in Aging
A long noncoding RNA called Lncbate1 regulates lipid synthesis in white adipose tissue during aging by modulating a microRNA-protein axis. This molecular mechanism reveals how aging alters fat storage and mobilization, with implications for metabolic decline and age-related disease prevention.
SIRT1 Downregulation by Advanced Glycation End Products Activates RANKL‐Dependent Osteoclast Signaling and Drives Chondrocyte Senescence During Osteoarthritis Development
Advanced glycation end products suppress SIRT1 expression in osteoclasts, triggering RANKL-dependent bone resorption and accelerated chondrocyte senescence—a mechanism that directly couples metabolic stress to cartilage degradation in osteoarthritis. This pathway represents a biochemical link between systemic glucose metabolism and joint degeneration, suggesting that metabolic control earlier in life may alter osteoarthritis trajectory.
Myostatin inhibitors preserve muscle mass during GLP-1 weight loss
NorthStrive Biosciences has filed patent applications for two therapeutic candidates designed to preserve lean muscle mass during GLP-1-mediated weight loss and other catabolic states. The compounds target myostatin and activin A pathways through peptide and probiotic delivery mechanisms, addressing a significant gap in current obesity pharmacotherapy where muscle loss accompanies fat loss.
A Cluster of Three snoRNAs Including Jouvence Required in the Gut Determines Lifespan and Confers Neuroprotection Through Metabolic Parameters
A cluster of three small nucleolar RNAs in the gut epithelium regulates lipid and sterol metabolism, with direct effects on lifespan and neuroprotection in aging. Disruption of these snoRNAs causes metabolic dysregulation that leads to neurodegeneration, while restoration in gut cells alone is sufficient to reverse these effects.
Regulatory RNA Sustains Liver Immunity and Metabolism in Aging
A regulatory RNA molecule specific to immune T cells sustains metabolic balance and immune function in the aging liver, addressing a fundamental mechanism of age-related decline. This correction validates findings on how the body maintains coordinated immune and metabolic signaling during aging.
SIRT3 blocks trained immunity, halting stem cell aging
SIRT3 suppression of hematopoietic stem cell aging prevents the development of trained immunity — a maladaptive immune memory state that drives chronic inflammation and tissue dysfunction. This mechanism directly links stem cell aging to the inflammatory cascade underlying age-related disease.
Multiomic single-cell perturbation screens reveal critical lncRNA regulators of senescence
A systematic screen of 32 aging-associated long non-coding RNAs identified HOTAIRM1 as a critical regulator of DNA repair pathways, with restoration of HOTAIRM1 in aged mouse lungs reducing fibrosis. This work establishes lncRNA regulation as a targetable mechanism in cellular senescence.
Additional Cover
APOE2, a rare genetic variant associated with exceptional longevity, activates cellular signaling pathways in neurons that resist senescence and maintain regenerative capacity. This finding identifies a molecular mechanism through which genetic variants can extend healthspan by preserving neuronal function and preventing age-related cellular decline.
FAM162A Is a Key Regulator of Mitochondrial Structure, Dynamics, and Bioenergetics, Driving Cellular Protection and Longevity
FAM162A, a mitochondrial cristae protein, regulates mitochondrial structure and energy production through interaction with OPA1, enhancing cellular stress resistance and extending lifespan in model organisms. This identifies a previously unrecognized mechanism linking mitochondrial dynamics to organismal longevity.
Sex Differences in Cognitive Aging: Caloric Restriction and Butyrate
Lifelong caloric restriction combined with sodium butyrate—a short-chain fatty acid—produces sex-specific effects on cognition and metabolism in aging rats, with females showing greater cognitive preservation and males demonstrating enhanced metabolic flexibility. These findings suggest that interventions affecting energy availability and gut-derived metabolites may influence aging trajectories differently across biological sexes.
Molecular insight into transcriptome profiling of aerobic exercise induced changes in aged skeletal muscle
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.
Mitrix moves mitochondria into the clinic
Mitrix Bio has reported preliminary Phase 1 safety data from mitochondrial transplantation in two older adults with no observed adverse effects, while simultaneously launching clinics offering the intervention under Right to Try frameworks. This represents a transition from preclinical work to early clinical deployment, though data density remains limited relative to narrative momentum.
Aging Triggers an Intestinal Energy Crisis and HDL3 Deficiency Disrupting Gut–Liver Axis Homeostasis
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.
Circulating levels of insulin-like growth factor binding protein 7 are associated with risks of chronic diseases and death
Circulating insulin-like growth factor binding protein 7 (IGFBP7) independently predicts risk of chronic disease and mortality across multiple conditions, suggesting it functions as a systemic biomarker of aging and physiological decline. Measurement of IGFBP7 may offer clinicians a quantifiable indicator of disease susceptibility that extends beyond traditional risk factors.