Calorie restriction is the most reasonable anti-ageing intervention: a meta-analysis of survival curves

Abstract

Despite technological advances, the survival records from longevity experiments remain the most indispensable tool in ageing-related research. A variety of interventions, including medications, genetic manipulations and calorie restriction (CR), have been demonstrated to extend the lifespan of several species. Surprisingly, few systematic studies have investigated the differences among these anti-ageing strategies using survival data. Here, we conduct a comprehensive and comparative meta-analysis of numerous published studies on Caenorhabditis elegans and Drosophila. We found that CR and genetic manipulations are generally more effective than medications at extending the total lifespan in both models, and CR can improve the ageing pattern of C. elegans. We further analysed the survival variation for different anti-ageing medications and determined that hypoglycaemic agents and antioxidants are advantageous despite only moderately increasing the overall lifespan; therefore, these two types of medications are promising CR mimetics. Analysis of genetic manipulations also indicated that the genes or pathways that extend lifespan in a healthier pattern are associated with CR. These results suggest that CR or CR mimetics may be the most reasonable and potentially beneficial anti-ageing strategy.

Figure 1

Schematic diagram of the cluster features. (A–C) Different anti-ageing effect patterns (e.g., salicylic acid: sharp improvement, ks61: slow improvement, N2 GD1: parallel improvement). (D) Size improvement. (E) Anti-ageing type features. (F) Boxplot of the visualized features of resveratrol and other treatments in C. elegans demonstrating that the survival curves generated using identical factors have similar features.

Figure 2

Analysis of different classes indicating that CR is more effective at changing the shape and scale of the survival curves. (A) Cumulative distribution of the size improvement in C. elegans. (B) Cumulative distribution of the type ratio in C. elegans. (C) Average case-control difference curves of C. elegans. (D) Cumulative distribution of the size improvement in Drosophila. (E) Cumulative distribution of the type ratio in Drosophila. (F) Average case-control difference curves of Drosophila.

Figure 3

Analysis of different medications demonstrating that antioxidants and hyperglycaemic agents extend the lifespan of both models more effectively than other medications. (A) Visualized scatter distribution of different medications classified by the size improvement and type in C. elegans. (B) Cumulative distribution of the size improvements due to medications in C. elegans. (C) Cumulative distribution of the type features due to medications in C. elegans. (D) Average case-control difference curves of C. elegans. (E) Visualized scatter distribution of different medications classified by the size improvement and type in Drosophila. (F) Cumulative distribution of the size improvement due to medications in Drosophila. (G) Cumulative distribution of the type features due to medications in Drosophila. (H) Average case-control difference curves of Drosophila.

Figure 4

Analysis of genetic manipulations in Drosophila indicates that CR-associated genes extend lifespan in a better pattern than other analysed genes. (A) Visualized feature distribution of genes: selected genes (orange) and other genes (cyan). (B) Significantly enriched GO terms (only term ontologies with corrected P-values (Benjamin) ≤ 0.01 are shown).

Figure 5

Graphical summary of the main results of our study. The effects of different anti-ageing interventions exhibited fairly strong species transitivity from C. elegans to Drosophila.