Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms

Emily L. Goldberg, Melissa J. Romero-Aleshire, Kristin R. Renkema, Melissa S. Ventevogel, Wade M. Chew, Jennifer L. Uhrlaub, Megan J Smithey, Kirsten Limesand, Gregory D. Sempowski, Heddwen L Brooks, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)130-138
Number of pages9
JournalAging Cell
Volume14
Issue number1
DOIs
StatePublished - Feb 1 2015

Fingerprint

Caloric Restriction
Adaptive Immunity
Sirolimus
T-Lymphocytes
Immune System
West Nile virus
Immune System Diseases
Virus Diseases
Thymus Gland
Communicable Diseases
Maintenance
Morbidity
Mortality
Population

Keywords

  • Anti-aging
  • Caloric restriction
  • Cellular immunology
  • Longevity regulation
  • Mouse models
  • T cell

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Goldberg, E. L., Romero-Aleshire, M. J., Renkema, K. R., Ventevogel, M. S., Chew, W. M., Uhrlaub, J. L., ... Nikolich-Zugich, J. (2015). Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell, 14(1), 130-138. https://doi.org/10.1111/acel.12280

Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. / Goldberg, Emily L.; Romero-Aleshire, Melissa J.; Renkema, Kristin R.; Ventevogel, Melissa S.; Chew, Wade M.; Uhrlaub, Jennifer L.; Smithey, Megan J; Limesand, Kirsten; Sempowski, Gregory D.; Brooks, Heddwen L; Nikolich-Zugich, Janko.

In: Aging Cell, Vol. 14, No. 1, 01.02.2015, p. 130-138.

Research output: Contribution to journalArticle

Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, Uhrlaub JL et al. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell. 2015 Feb 1;14(1):130-138. https://doi.org/10.1111/acel.12280
Goldberg, Emily L. ; Romero-Aleshire, Melissa J. ; Renkema, Kristin R. ; Ventevogel, Melissa S. ; Chew, Wade M. ; Uhrlaub, Jennifer L. ; Smithey, Megan J ; Limesand, Kirsten ; Sempowski, Gregory D. ; Brooks, Heddwen L ; Nikolich-Zugich, Janko. / Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. In: Aging Cell. 2015 ; Vol. 14, No. 1. pp. 130-138.
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