title: Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression.
abstract: We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR(Δ/Δ)) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTOR(Δ/Δ) mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR(Δ/Δ) mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR(Δ/Δ) mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Edmund B
authors.initials: EB
authors.lastname: Chen
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wang
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.forename: Nisha
authors.initials: N
authors.lastname: Narayan
authors.forename: Marie M
authors.initials: MM
authors.lastname: Fergusson
authors.forename: Ilsa I
authors.initials: II
authors.lastname: Rovira
authors.forename: Michele
authors.initials: M
authors.lastname: Allen
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Springer
authors.forename: Cory U
authors.initials: CU
authors.lastname: Lago
authors.forename: Shuling
authors.initials: S
authors.lastname: Zhang
authors.forename: Wendy
authors.initials: W
authors.lastname: DuBois
authors.forename: Theresa
authors.initials: T
authors.lastname: Ward
authors.forename: Rafael
authors.initials: R
authors.lastname: deCabo
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Beverly
authors.initials: B
authors.lastname: Mock
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D008136:Longevity / Q000502:physiology*; D008297:Male; D008322:Mammals; D051379:Mice; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D005947:Glucose