title: Do altered energy metabolism or spontaneous locomotion 'mediate' decelerated senescence?
abstract: That one or multiple measures of metabolic rate may be robustly associated with, or possibly even causative of, the progression of aging-resultant phenotypes such as lifespan is a long-standing, well-known mechanistic hypothesis. To broach this hypothesis, we assessed metabolic function and spontaneous locomotion in two genetic and one dietary mouse models for retarded aging, and subjected the data to mediation analyses to determine whether any metabolic or locomotor trait could be identified as a mediator of the effect of any of the interventions on senescence. We do not test the hypothesis of causality (which would require some experiments), but instead test whether the correlation structure of certain variables is consistent with one possible pathway model in which a proposed mediating variable has a causal role. Results for metabolic measures, including oxygen consumption and respiratory quotient, failed to support this hypothesis; similar negative results were obtained for three behavioral motion metrics. Therefore, our mediation analyses did not find support that any of these correlates of decelerated senescence was a substantial mediator of the effect of either of these genetic alterations (with or without caloric restriction) on longevity. Further studies are needed to relate the examined phenotypic characteristics to mechanisms of aging and control of longevity.
authors.affiliation: Department of Internal Medicine, Southern Illinois University-School of Medicine, Springfield, IL, 62794, USA.
authors.forename: Oge
authors.initials: O
authors.lastname: Arum
authors.forename: John Alexander
authors.initials: JA
authors.lastname: Dawson
authors.forename: Daniel Larry
authors.initials: DL
authors.lastname: Smith
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
mesh_terms: D000375:Aging; D000818:Animals; D031204:Caloric Restriction / Q000379:methods; D004734:Energy Metabolism / Q000502:physiology*; D008124:Locomotion / Q000502:physiology*; D008136:Longevity / Q000235:genetics; D051379:Mice; D010101:Oxygen Consumption / Q000502:physiology
keywords: caloric restriction; gas-exchange (indirect calorimetry) metabolism; growth hormone hormonal signaling; mediation analysis; physiology of longevity; spontaneous physical activity