Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging
Bobba-Alves N, Sturm G, Lin J, Ware S, Karan K, Monzel A, Bris C, Procaccio V, Lenaers G, Higgins-Chen A, Levine M, Horvath S, Santhanam B, Kaufman B, Hirano M, Epel E, Picard M. Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging. Psychoneuroendocrinology 2023, 155: 106322. PMID: 37423094, PMCID: PMC10528419, DOI: 10.1016/j.psyneuen.2023.106322.Peer-Reviewed Original ResearchConceptsCellular agingCellular energy expenditureDNA methylation clockMitochondrial oxidative phosphorylationStress adaptationMtDNA instabilityOXPHOS activityMethylation clockOxidative phosphorylationMetabolic shiftEnergetic costHuman fibroblast lineCellular basisPhysiological responsesFibroblast linesStress triggersPotential driversBiological agingEnergy expenditureChronic activationLifespanDamaging effectsPrimary human fibroblast linesCytokine secretionPhosphorylationOxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases
Sturm G, Karan K, Monzel A, Santhanam B, Taivassalo T, Bris C, Ware S, Cross M, Towheed A, Higgins-Chen A, McManus M, Cardenas A, Lin J, Epel E, Rahman S, Vissing J, Grassi B, Levine M, Horvath S, Haller R, Lenaers G, Wallace D, St-Onge M, Tavazoie S, Procaccio V, Kaufman B, Seifert E, Hirano M, Picard M. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Communications Biology 2023, 6: 22. PMID: 36635485, PMCID: PMC9837150, DOI: 10.1038/s42003-022-04303-x.Peer-Reviewed Original ResearchConceptsIntegrated stress responseOXPHOS defectsMitochondrial diseaseCellular energy expenditureMitochondrial DNA instabilityPatient-derived fibroblastsMitochondrial oxidative phosphorylationCell divisionExtracellular secretionOxidative phosphorylationStress responseDNA instabilityMechanistic basisEnergetic costEpigenetic agingGeneral mechanismOXPHOSBiological agingExcess energy expenditurePotential mechanismsEnergy expenditureCellsMulti-system disorderMetabokinesRNAseq