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Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice.

Kan XieHelmut FuchsEnzo ScifoDan LiuNasir Ahmad AzizJuan Antonio Aguilar-PimentelOana Veronica AmarieLore BeckerPatricia da Silva-ButtkusJulia Calzada-WackYi-Li ChoYushuang DengA Cole EdwardsLillian GarrettChristina GeorgopoulouRaffaele GerliniSabine Maria HölterTanja Klein-RodewaldMichael KramerStefanie LeuchtenbergerDimitra LountziPhillip Mayer-KuckukLena L NoverManuela A OestereicherClemens OverkottBrandon L PearsonBirgit RathkolbJan RozmanJenny RussKristina SchaafNadine SpielmannAdrián Sanz-MorenoClaudia StoegerIrina TreiseDaniele BanoDirk H BuschJochen GrawMartin KlingensporFlorentine RadelfahrBeverly A MockPaolo SalomoniCarsten B Schmidt-WeberMarco WeiergräberEckhard WolfWolfgang WurstValérie Gailus-DurnerMonique M B BretelerMartin Hrabě de AngelisDan Ehninger
Published in: Nature communications (2022)
Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice. For each phenotype, we establish lifetime profiles to determine when age-dependent change is first detectable relative to the young adult baseline. We examine key lifespan regulators (putative anti-aging interventions; PAAIs) for a possible countering of aging. Importantly, unlike most previous studies, we include in our study design young treated groups of animals, subjected to PAAIs prior to the onset of detectable age-dependent phenotypic change. Many PAAI effects influence phenotypes long before the onset of detectable age-dependent change, but, importantly, do not alter the rate of phenotypic change. Hence, these PAAIs have limited effects on aging.
Keyphrases
  • young adults
  • physical activity
  • gene expression
  • high throughput
  • depressive symptoms
  • high fat diet induced
  • transcription factor
  • genome wide
  • metabolic syndrome
  • skeletal muscle
  • newly diagnosed