Delay of T Cell Senescence by Caloric Restriction in Aged Long-Lived Nonhuman Primates

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 im...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-12, Vol.103 (51), p.19448-19453
Main Authors: Messaoudi, Ilhem, Warner, Jessica, Fischer, Miranda, Park, Buyng, Hill, Brenna, Mattison, Julie, Lanes, Mark A., Roth, George S., Ingram, Donald K., Picker, Louis J., Douek, Daniel C., Mori, Motomi, Nikolich-Žugich, Janko
Format: Article
Language:English
Subjects:
Age Factors
Aging
Animals
Biological Sciences
Blood
Caloric Restriction
Cell Count
Cellular Senescence - immunology
Cellular Senescence - physiology
Cytokines
Cytokines - metabolism
Female animals
Flow Cytometry
Histograms
Immune system
Macaca mulatta
Male animals
Memory
Nutrition
Primates
Receptors, Antigen, T-Cell - metabolism
Rodents
T cell antigen receptors
T cell receptors
T lymphocytes
T-Lymphocytes - immunology
T-Lymphocytes - physiology
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Summary: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 naive 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0606661103