Every article, presentation, spotlight, and news item we've tagged to Metabolic Pathways.
Showing 49–72 of 77
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.
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.
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 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 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.
APOE2, a genetic variant associated with exceptional longevity, activates DNA repair pathways and resists cellular senescence in neurons, while APOE4 exhibits elevated DNA damage and senescence markers. This mechanism extends beyond lipid metabolism, explaining APOE2's protective effects against neurodegeneration.
Researchers identified a hierarchical gene regulatory network controlling yeast lifespan, where peripheral genes act through master regulators that converge on functional modules governing stress response, autophagy, and proteostasis. This architecture provides a framework for dissecting genetic complexity in aging and maps directly to mechanisms that influence human longevity pathways.
Early-life consumption of galactose and glucose (lactose components) extends lifespan in female flies exposed to obesogenic diets in adulthood through reprogramming of lipid metabolism, while reducing lifespan in males. This nutritional programming effect demonstrates that early dietary composition establishes metabolic resilience patterns that persist throughout life and respond differentially by sex.
Aged male mice maintain glucose tolerance despite accumulating more fat on a high-fat diet than younger counterparts, a metabolic uncoupling driven by increased energy storage efficiency and reduced lipid turnover. This finding indicates that obesity and glucose dysregulation diverge with age, presenting distinct intervention targets for metabolic health in older populations.
D-pinitol, a naturally occurring inositol derivative, extends lifespan in C. elegans by coordinating three distinct cellular mechanisms: antioxidant defense, protein stability (proteostasis), and autophagy. This multi-pathway activation suggests a compound that addresses fundamental aging processes rather than targeting a single intervention point.
This correction addresses methodological refinements in research demonstrating that monoamine oxidase-A drives stress-induced cellular aging by disrupting the cell's ability to clear damaged mitochondria. The finding clarifies a direct mechanism linking stress response dysfunction to accelerated senescence at the mitochondrial level.
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.
PX578, a first-in-class small molecule activator of mitochondrial DNA polymerase gamma, demonstrated preclinical efficacy in restoring mitochondrial DNA levels and cellular energy production across multiple POLG disease models. The compound addresses the underlying genetic defect in mitochondrial DNA depletion syndromes, for which no disease-modifying treatments currently exist.
Pulmatrix and Eos SENOLYTIX are merging to develop PTC-2105, a candidate designed to modulate mitochondrial function and clear senescent cells in sarcopenia and metabolic disease. The transaction signals a fundamental shift in biopharma toward targeting aging biology directly rather than its downstream manifestations.
Phosphoenolpyruvate, a glycolytic metabolite, suppresses cGAS-STING-driven inflammation and improves cognitive function in Alzheimer's disease models while correlating with healthy aging markers in humans. This identifies a metabolic checkpoint that regulates innate immune signaling during aging.
Blocking growth hormone signaling specifically in adipose tissue reduces neuroinflammation, preserves synaptic integrity, and improves cognitive performance across multiple domains in aged mice. This identifies peripheral adipose tissue as an unexpected regulator of brain aging, suggesting a therapeutic target for age-related cognitive decline.
Circulating small RNAs, particularly nine piRNAs, predict two-year survival in older adults with greater accuracy than age and clinical factors alone, with experimental evidence suggesting reduced piRNA levels associate with extended lifespan. These findings identify specific small RNA signatures as measurable biomarkers and potential therapeutic targets for longevity interventions.
FGF21, a growth factor that declines with age, delays intervertebral disc degeneration by upregulating SIRT1 and restoring mitochondrial quality control through the PINK1-Parkin mitophagy pathway. This mechanism addresses a primary driver of age-related lower back pain by counteracting cellular senescence in disc tissue.
Triple and dual agonist drugs like retatrutide and CagriSema target multiple metabolic pathways simultaneously, producing weight loss exceeding 20-30% in clinical trials. These medications represent a shift toward precision metabolic intervention, with implications for both obesity management and aging-related cellular stress.
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.
HKDC1, a metabolic enzyme, declines with age due to chromatin remodeling that blocks its transcription factor regulation, and this decline correlates with cognitive impairment and neurodegeneration in both mice and humans. Loss of HKDC1 compromises mitochondrial integrity and triggers neuroinflammation, establishing a mechanistic link between metabolic gene silencing and age-related neurological decline.
FGF21 activates a cellular repair pathway in spinal disc cells by upregulating SIRT1, which deacetylates FOXO3 and triggers mitochondrial autophagy, thereby suppressing cell senescence and slowing intervertebral disc degeneration. This identifies a targetable molecular axis with direct relevance to preventing age-related spinal structural decline and associated disability.
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.
Partial cellular reprogramming using three Yamanaka factors (OSK) successfully restored memory function in aged mice and Alzheimer's disease models by rejuvenating memory-encoding neurons while preserving their neuronal identity. This approach demonstrates that targeted reprogramming of engram cells can reverse age-related cognitive decline without causing dedifferentiation or memory loss.
