Every article, presentation, spotlight, and news item we've tagged to Metabolic Pathways.
Showing 25–48 of 77
Caloric restriction reduces circulating C3a, a complement protein that drives inflammaging in aged tissues. This identifies a specific immunometabolic pathway through which moderate energy restriction extends healthspan in humans.
Fasting and caloric restriction activate ADIOL, a steroid hormone that signals through estrogen receptor β to reduce kynurenic acid in the nervous system and improve healthspan independent of lifespan extension. This mechanism appears evolutionarily conserved and remains effective even when ADIOL is supplemented late in life.
Nuchido addresses NAD+ decline through targeted restoration of the salvage pathway rather than simple precursor replacement, supported by randomized controlled human trials demonstrating improvements in inflammation, glycation, and biological age markers. This systems-biology approach represents a maturation of the NAD+ intervention landscape toward mechanistic rather than marketing-driven solutions.
Aging amplifies the liver's inflammatory and metabolic response to high-fat diet, increasing hepatic steatosis and transcriptional dysregulation. Rapamycin treatment reversed most diet-driven gene expression changes in older mice, reducing steatosis, body weight gain, and markers associated with liver disease progression.
Researchers demonstrated that combining NMN supplementation with apigenin—which inhibits NAD+ breakdown—restores muscle function and bone structure in aged mice. This dual approach addresses both supply and preservation of NAD+, a critical coenzyme in cellular energy metabolism and stress resistance.
Researchers demonstrated that combining NAD+ precursor supplementation (NMN) with apigenin, a compound that reduces NAD+ degradation, restores muscle function and bone structure in aged mice. This dual-mechanism approach addresses both NAD+ availability and preservation, with relevance to human aging given prior clinical evidence for NAD+ precursors in metabolic and respiratory function.
Research published in PNAS Nexus proposes that autophagy dysfunction—a slowdown in cellular recycling—precedes amyloid and tau pathology in Alzheimer's disease. This upstream mechanism shifts the therapeutic target from clearing late-stage debris to restoring the cell's natural cleanup capacity earlier in disease progression.
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.
Fasting activates mitochondrial and endothelial repair mechanisms that reverse markers of vascular aging, with implications for extending healthspan through metabolic intervention. The research demonstrates that structured fasting protocols can restore cellular energy production and vascular function independent of weight loss.
A randomized, placebo-controlled trial in sedentary adults aged 65-85 found that weekly rapamycin (6 mg) blunted functional gains from a 13-week exercise program, with the placebo group showing greater improvements in chair-stand performance and related measures. The drug's 62-hour half-life likely prevented adequate recovery of mTORC1 signaling between training sessions, creating a pharmacokinetic conflict with exercise adaptation.
Terbinafine and miglustat, FDA-approved drugs, extend lifespan and healthspan by inducing mitochondrial stress responses through coordinated activation of ATFS-1 and DAF-16 pathways. This mechanism represents a distinct integration of mitochondrial and insulin signaling stress responses relevant to aging intervention.
SRN-901, a five-component oral combination therapy, demonstrated a 33% increase in median lifespan and 70% reduction in frailty progression in mice, with preserved physical function and reduced tumor incidence. The multi-pathway approach contrasts with single-target interventions, suggesting that aging requires simultaneous modulation of interconnected biological processes rather than isolated molecular manipulation.
SRN-901, an oral combinatorial drug, extended median remaining lifespan by 33% in aged mice on a Western diet, with a 46% reduction in hazard of death and 70% attenuation of frailty progression. Multi-omics analysis indicated upregulation of DNA repair and metabolic pathways alongside suppression of inflammatory and oxidative stress responses.
Renue by Science received recognition for its Total NAD+ Restoration Protocol, a multi-pathway supplement approach designed to address age-related NAD+ decline through enhanced precursor delivery, reduced NAD+ catabolism, improved mitochondrial efficiency, and cellular repair support. NAD+ restoration represents a targeted intervention in the metabolic foundation of cellular aging.
Reduced insulin signaling extends lifespan in Drosophila, but the effect—beneficial or detrimental—depends on the genetic interaction between mitochondrial and nuclear DNA. This reveals that conserved aging mechanisms operate differently across individuals based on mito-nuclear epistasis, with direct implications for personalized longevity interventions.
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'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.
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—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 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.
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.
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.
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.
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.
