title: Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms.
abstract: Aging of the world population and a concomitant increase in age-related diseases and disabilities mandates the search for strategies to increase healthspan, the length of time an individual lives healthy and productively. Due to the age-related decline of the immune system, infectious diseases remain among the top 5-10 causes of mortality and morbidity in the elderly, and improving immune function during aging remains an important aspect of healthspan extension. Calorie restriction (CR) and more recently rapamycin (rapa) feeding have both been used to extend lifespan in mice. Preciously few studies have actually investigated the impact of each of these interventions upon in vivo immune defense against relevant microbial challenge in old organisms. We tested how rapa and CR each impacted the immune system in adult and old mice. We report that each intervention differentially altered T-cell development in the thymus, peripheral T-cell maintenance, T-cell function and host survival after West Nile virus infection, inducing distinct but deleterious consequences to the aging immune system. We conclude that neither rapa feeding nor CR, in the current form/administration regimen, may be optimal strategies for extending healthy immune function and, with it, lifespan.
authors.affiliation: Departments of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA; Department of Nutritional Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Goldberg
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Romero-Aleshire
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Renkema
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Ventevogel
authors.forename: Wade M
authors.initials: WM
authors.lastname: Chew
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Uhrlaub
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Smithey
authors.forename: Kirsten H
authors.initials: KH
authors.lastname: Limesand
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Heddwen L
authors.initials: HL
authors.lastname: Brooks
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Žugich
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D031204:Caloric Restriction; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects; D014901:West Nile Fever / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000502:physiology
chemical_list: D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: T cell; anti-aging; caloric restriction; cellular immunology; longevity regulation; mouse models