Metabolic Pathways Library
Every article, presentation, spotlight, and news item we've tagged to Metabolic Pathways.
Showing 49–72 of 148
Correction to “An Ad Libitum‐Fed Diet That Matches the Beneficial Lifespan Effects of Caloric Restriction but Acts via Opposite Effects on the Energy‐Splicing Axis”
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.
Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging
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 an ADIOL‐NHR‐91‐Kynurenine Pathway Signaling Axis to Promote Healthspan
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.
Fasting-Mimicking Diet Reverses Metabolic Disease Through Cellular Repair
Fasting-mimicking diets trigger autophagy and cellular regeneration through a precise five-day protocol, with clinical evidence demonstrating reversal of insulin resistance and reduced medication dependency in metabolic disease. The mechanism operates as a repair system distinct from emergency symptom management—the body's inherent capacity to reorganize damaged tissue during the refeeding phase.
Nuchido announced as Catalyst Partner for The Longevity Show
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.
Rapamycin Reverses the Hepatic Response to Diet‐Induced Metabolic Stress That Is Amplified by Aging
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.
A Combination NAD+ Treatment Has Benefits for Mice
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.
A Combination NAD+ Treatment Has Benefits for Mice
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.
Autophagy angle sharpens Anavex’s investment case for Alzheimer’s
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.
Time-Restricted Eating Extends Male Lifespan Without Systemic Changes
An 8-hour time-restricted feeding window extended median lifespan in male mice by 12%, independent of measurable changes in systemic metabolic or inflammatory markers. The effect appears sex-dependent and decoupled from the caloric restriction that typically accompanies feeding time windows in females.
$30.8m funds Cambrian Bio’s bid to preserve resilience in aging
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.
Additional Cover
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.
Rapamycin Might Blunt Exercise Response in Humans
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.
TORC1 Modulation Brings Aging Biology to Skincare
Rapalogix has secured $20 million in Series A funding to commercialize Re-Q, a skincare line targeting TORC1 signaling—a cellular pathway central to aging biology. The investment reflects longevity biotech's shift toward tractable, measurable clinical endpoints and near-term commercial viability rather than abstract lifespan claims.
Protein Restriction Activates FGF21 Longevity Pathway
Moderate protein restriction activates fibroblast growth factor 21 (FGF21), improving metabolic efficiency and extending lifespan in animal models. This challenges prevailing high-protein recommendations for sedentary populations and suggests protein quantity requires context-specific calibration based on activity level and metabolic state.
Targeting Mitochondrial Stress Responses: Terbinafine and Miglustat as Novel Lifespan and Healthspan Modulators
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.
Disappointing results from the first rapamycin-plus-exercise trial
A randomized controlled trial combining rapamycin and exercise showed no significant improvement in physical function or body composition compared to exercise alone, challenging the hypothesis that mTOR inhibition enhances the adaptive response to resistance training in older adults.
Muscle epigenetic age reduction with NR supplementation
A pooled analysis of clinical trials and laboratory work found that five months of nicotinamide riboside supplementation correlated with approximately 2.5 years of reduction in muscle epigenetic age, measured by multiple clock algorithms. The finding suggests NAD+ precursor supplementation may influence age-related molecular signatures in skeletal muscle, though the company acknowledges results are preliminary and largely correlational.
New longevity drug SRN-901 shows 33% lifespan boost
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.
TORC1 inhibition advances skin longevity beyond cosmetic treatment
Rapalogix Health secured $20 million in Series A funding to expand its skincare line targeting TORC1, a cellular pathway implicated in skin aging. The company's approach addresses how cells regulate nutrient sensing and protein synthesis—processes that deteriorate with age and manifest visibly in skin structure and appearance.
Seragon study shows SRN-901 extends median lifespan in mice
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.
Autophagy Collapse Drives Sepsis Risk in Aging Kidneys
Aging kidneys show impaired autophagy activation—a cellular cleanup mechanism—making them vulnerable to sepsis-induced acute kidney injury. Restoring autophagy through TFEB activation or pharmacological intervention partially reverses this age-related deficit and protects against septic injury in aged tissues.
Renue by Science wins precision recovery & performance award
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.
Lifespan and Fecundity Impacts of Reduced Insulin Signalling Can Be Directed by Mito‐Nuclear Epistasis in Drosophila
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.