Comparative and meta-analytic insights into life extension via dietary restriction
Shinichi Nakagawa
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorMalgorzata Lagisz
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorKatie L. Hector
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorHamish G. Spencer
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorShinichi Nakagawa
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorMalgorzata Lagisz
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorKatie L. Hector
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorHamish G. Spencer
Department of Zoology, National Research Centre for Growth and Development, University of Otago, PO Box 56, Dunedin 9054, New Zealand
Search for more papers by this authorSummary
Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR–longevity relationship than evolutionary conservation although alternative explanations are possible.
Supporting Information
Fig. S1 A schematic showing typical survival curves for the control group and the DR group and time points we used to obtain information for calculating effect size values, ln(HR).
Fig. S2 A phylogenetic tree of the 36 species used in the analysis.
Fig. S3 Funnel plots of effect size, ln(HR), against its precision (the inverse of standard error, 1/SE). (A) The original effect sizes against the corresponding precision values. (B) Corrected effect sizes (from Model 6) against the precision. Asymmetry in the funnel shape is less obvious for the corrected data (B) than the original data (A).
Fig. S4 The effect of caloric intake and protein intake on the relationship between DR and survival. (A–B) Identical to Fig. 3 except that three additional outlier values are shown.
Fig. S5 Visualizing age-independent and age-dependent changes in mortality rate due to dietary restriction (DR) in terms of the natural logarithms of mortality rate and hazard ratio. (A-B) Age-independent mortality rate change. (C-D) Age-dependent mortality rate change. (E-F) Both types of mortality rate changes at work.
Table S1 Conversions among the natural logarithm of hazard ratio, ln(HR), hazard ratio, HR and percentage (%) difference.
Table S2 Estimates from Bayesian mixed-effects meta-analysis (Model 1) and phylogenetic mixed-effects meta-analysis (Model 2) for the relationship between DR and longevity, measured as ln(HR).
Table S3 Estimates from Bayesian mixed-effects meta-regression (Model 3) and phylogenetic mixed-effects meta-regression (Model 4) examining ‘sex’ effect and ‘model species’ effect on the relationship between DR and longevity, measured as ln(HR).
Table S4 Estimates from Egger’s regression analysis for the original data (Equations 14 to 16) and the adjusted data from Model 6 (Equations S17-18).
Table S5 Estimates from Bayesian mixed-effects meta-regression (Model 5) and phylogenetic mixed-effects meta-regression (Model 6) examining the effects of caloric and protein intake on the relationship between DR and longevity, measured by ln(HR).
Table S6 Estimates from meta-regression models (Models 7–14), testing additional predictors (for the details of each model, see Materials and Methods) by building upon Model 6 (Table S4).
Table S7 Estimates from Bayesian mixed-effects meta-regression for examining the age-independent mortality rate (Models 15 and 17 with the former having ‘species’ as a fixed factor and the latter species as a random factor) and the age-dependent mortality rate (Models 16 and 18) among the five model species.
Data S1 Main data file.
Data S2 Phylogenetic tree.
Data S3 Data with slope and intercept estimates.
Dialog S1 Additional experimental procedures and their details along with additional references.
Dialog S2 Details of Data S1-3 files.
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