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Rapamycin not dietary restriction improves resilience against pathogens: a meta-analysis

Phillips, Eleanor J., Simons, Mirre J. P.·2023·GeroScience
DOI 10.1007/s11357-022-00691-4PMC PMC9886774

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Abstract

Dietary restriction (DR) and rapamycin both increase lifespan across a number of taxa. Despite this positive effect on lifespan and other aspects of health, reductions in some physiological functions have been reported for DR, and rapamycin has been used as an immunosuppressant. Perhaps surprisingly, both interventions have been suggested to improve immune function and delay immunosenescence. The immune system is complex and consists of many components. Therefore, arguably, the most holistic measurement of immune function is survival from an acute pathogenic infection. We reanalysed published post-infection short-term survival data of mice ( n = 1223 from 23 studies comprising 46 effect sizes involving DR ( n = 17) and rapamycin treatment ( n = 29) and analysed these results using meta-analysis. Rapamycin treatment significantly increased post infection survival rate (lnHR = − 0.72; CI = − 1.17, -0.28; p = 0.0015). In contrast, DR reduced post-infection survival (lnHR = 0.80; CI = 0.08, 1.52; p = 0.03). Importantly, the overall effect size of rapamycin treatment was significantly lower ( p < 0.001) than the estimate from DR studies, suggesting opposite effects on immune function. Our results show that immunomodulation caused by rapamycin treatment is beneficial to the survival from acute infection. For DR, our results are based on a smaller number of studies, but do warrant caution as they indicate possible immune costs of DR. Our quantitative synthesis suggests that the geroprotective effects of rapamycin extend to the immune system and warrants further clinical trials of rapamycin to boost immunity in humans.

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Fig. 1 Forest plot of log hazard ratio estimates (circles) for DR and rapamycin post-infection survival curve pairings (n = 46) from Cox proportional hazard models. Squares indicate overall effect sizes as determined using meta-analysis controlling for interdependence of study and shared controls. Whiskers indicate 95% CIs
Fig. 1 Forest plot of log hazard ratio estimates (circles) for DR and rapamycin post-infection survival curve pairings (n = 46) from Cox proportional hazard models. Squares indicate overall effect sizes as determined using meta-analysis controlling for interdependence of study and shared controls. Whiskers indicate 95% CIsCC BY · PubMed Central

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Metadata

Authors
Phillips, E. J., & Simons, M. J. P.
ORCID
Simons, Mirre J. P.
Venue
GeroScience
Publisher
Springer Science and Business Media LLC
Published
2022-11-18
Volume
45
Issue
2
Pages
1263-1270
ISSN
  • 2509-2715
  • 2509-2723
DOI
10.1007/s11357-022-00691-4
PMC
PMC9886774
Cited by
21
References
9
Language
en
Licence
Funders
  • Wellcome Trust (216405/Z/19/Z)
  • Academy of Medical Sciences (SBF004\1085)

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