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

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.

Amino Acid Availability Is Not Essential for Life-Span Extension by Dietary Restriction in the Fly.

Dietary restriction (DR) is one of the most potent ways to extend health and life span. Key progress in understanding the mechanisms of DR, and aging more generally, was made when dietary protein, and more specifically essential amino acids (EAA), were identified as the dietary component to restrict to obtain DR's health and life-span benefits. This role of dietary amino acids has influenced work on aging mechanisms, especially in nutrient sensing, for example, Target of Rapamycin and insulin(-like) signaling networks. Experimental biology in Drosophila melanogaster has been instrumental in generating and confirming the hypothesis that EAA availability is important in aging. Here, we expand on previous work testing the involvement of EAA in DR through large-scale (N = 6 238) supplementation experiments across 4 diets and 2 genotypes in female flies. Surprisingly, we find that EAA are not essential to DR's life-span benefits. Importantly, we do identify the fecundity benefits of EAA supplementation suggesting the supplemented EAA were bioavailable. Furthermore, we find that the effects of amino acids on life span vary by diet and genetic line studied and that at our most restricted diet fecundity is constrained by other nutrients than EAA. We suggest that DR for optimal health is a concert of nutritional effects, orchestrated by genetic, dietary, and other environmental interactions. Our results question the universal importance of amino acid availability in the biology of aging and DR.

What does carotenoid-dependent coloration tell? Plasma carotenoid level signals immunocompetence and oxidative stress state in birds-A meta-analysis.

Mechanisms maintaining honesty of sexual signals are far from resolved, limiting our understanding of sexual selection and potential important parts of physiology. Carotenoid pigmented visual signals are among the most extensively studied sexual displays, but evidence regarding hypotheses on how carotenoids ensure signal honesty is mixed. Using a phylogenetically controlled meta-analysis of 357 effect sizes across 88 different species of birds, we tested two prominent hypotheses in the field: that carotenoid-dependent coloration signals i) immunocompetence and/or ii) oxidative stress state. Separate meta-analyses were performed for the relationships of trait coloration and circulating carotenoid level with different measures of immunocompetence and oxidative stress state. For immunocompetence we find that carotenoid levels (r = 0.20) and trait color intensity (r = 0.17) are significantly positively related to PHA response. Additionally we find that carotenoids are significantly positively related to antioxidant capacity (r = 0.10), but not significantly related to oxidative damage (r = -0.02). Thus our analyses provide support for both hypotheses, in that at least for some aspects of immunity and oxidative stress state the predicted correlations were found. Furthermore, we tested for differences in effect size between experimental and observational studies; a larger effect in observational studies would indicate that co-variation might not be causal. However, we detected no significant difference, suggesting that the relationships we found are causal. The overall effect sizes we report are modest and we discuss potential factors contributing to this, including differences between species. We suggest complementary mechanisms maintaining honesty rather than the involvement of carotenoids in immune function and oxidative stress and suggest experiments on how to test these.