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

Aging Cell

Emily L. Goldberg²  Melissa J. Romero-Aleshire¹  Kristin R. Renkema²  Melissa S. Ventevogel⁴  Wade M. Chew³  Jennifer L. Uhrlaub²  Megan J. Smithey²  Kirsten H. Limesand⁵  Gregory D. Sempowski⁴  Heddwen L. Brooks¹ 

[1] Department of Physiology, University of Arizona College of Medicine, Tucson, AZ, USA;Departments of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA;Arizona Cancer Center, University of Arizona College of Medicine, Tucson, AZ, USA;Human Vaccine Institute, Duke University, Durham, NC, USA;Department of Nutritional Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ, USA

关键词: anti‐aging;    cellular immunology;    caloric restriction;    longevity regulation;    mouse models;    T cell;   

DOI  :  10.1111/acel.12280

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.