title: Rapamycin increases grip strength and attenuates age-related decline in maximal running distance in old low capacity runner rats.
abstract: Rapamycin is known to extend lifespan. We conducted a randomized placebo-controlled study of enteric rapamycin-treatment to evaluate its effect on physical function in old low capacity runner (LCR) rats, a rat model selected from diverse genetic background for low intrinsic aerobic exercise capacity without genomic manipulation and characterized by increased complex disease risks and aging phenotypes. The study was performed in 12 male and 16 female LCR rats aged 16-22 months at baseline. The treatment group was fed with rapamycin-containing diet pellets at approximately 2.24mg/kg body weight per day and the placebo group with the same diet without rapamycin for six months. Observation was extended for additional 2 months. Physical function measurements include grip strength measured as maximum tensile force using a rat grip strength meter and maximum running distance (MRD) using rat physical treadmill test. The results showed that rapamycin improved grip strength by 13% (p=.036) and 60% (p=.001) from its baseline in female and male rats, respectively. Rapamycin attenuated MRD decline by 66% (p=.001) and 46% (p=.319) in females and males, respectively. These findings provide initial evidence for beneficial effect of rapamycin on physical functioning in an aging rat model of high disease risks with significant implication in humans.
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.|Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Xue
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Huanle
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Abadir
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Tyesha N
authors.initials: TN
authors.lastname: Burks
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Carlson
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.|Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.affiliation: Department of Medicine Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D018737:Hand Strength / Q000502:physiology*; D008297:Male; D053580:Muscle Strength / Q000187:drug effects* / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012420:Running / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D020123:Sirolimus
keywords: aging; healthspan; low capacity runner rats; physical function; rapamycin