title: Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates.
abstract: Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decreases mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. In rodents, CR was reported to delay the aging of the immune system (immune senescence), which is believed to be largely responsible for a dramatic increase in age-related susceptibility to infectious diseases. However, it is unclear whether CR can exert similar effects in long-lived organisms. Previous studies involving 2- to 4-year CR treatment of long-lived primates failed to find a CR effect or reported effects on the immune system opposite to those seen in CR-treated rodents. Here we show that long-term CR delays the adverse effects of aging on nonhuman primate T cells. CR effected a marked improvement in the maintenance and/or production of naïve T cells and the consequent preservation of T cell receptor repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells. Our results provide evidence that CR can delay immune senescence in nonhuman primates, potentially contributing to an extended lifespan by reducing susceptibility to infectious disease.
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
authors.forename: Jessica
authors.initials: J
authors.lastname: Warner
authors.forename: Miranda
authors.initials: M
authors.lastname: Fischer
authors.forename: Buyng
authors.initials: B
authors.lastname: Park
authors.forename: Brenna
authors.initials: B
authors.lastname: Hill
authors.forename: Julie
authors.initials: J
authors.lastname: Mattison
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lane
authors.forename: George S
authors.initials: GS
authors.lastname: Roth
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Zugich
mesh_terms: D000367:Age Factors; D000818:Animals; D031204:Caloric Restriction; D002452:Cell Count; D016922:Cellular Senescence / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D008253:Macaca mulatta; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell