The practice of calorie restriction slows aging in near all species and lineages tested to date. It produces significant health benefits in humans. Unfortunately the gain in life span scales down as species life span scales up. While calorie restriction extends maximum life span in mice and median life span in short-lived, small primates by 40% or more, it is not likely to have an effect size of more than five years when it comes to human life spans. That said, calorie restriction is by far the most robust and well tested of the few means available to adjust life span. Is it, however, as the authors of this paper would have it, the "most reasonable anti-aging intervention?"
Reliability is good, but size of effect is also important. Calorie restricted individuals still age and die on much the same schedule as the rest of us, just a fraction less rapidly. Good health practices can't add decades to life: three quarters of the healthiest people are dead by age 90, even given access to the best of medical technology over the course of the past half century. Calorie restriction, like exercise, is something that everyone should consider because it is essentially free, and has some benefit. But future life spans will be determined by new medical technology such as senolytic therapies, built on the SENS model of repairing the damage that causes aging, not by calorie restriction or recreation of some of its effects via pharmaceuticals.
Research on the biology of ageing has been conducted for centuries. Survival curves showing the surviving proportion of a population versus time are an intuitive means of illustrating the whole lifespan of a group of organisms and remain a key component of ageing research. Various anti-ageing interventions have been demonstrated to extend the lifespan of model organisms ranging from nematodes to fruit flies to rodents, with contradictory reports in rhesus monkeys. These interventions have mainly included calorie restriction (CR), genetic manipulations, and pharmaceutical administration.
However, whether these interventions extend the lifespan via universal or distinct patterns remains unclear. Traditionally, in ageing research, survival data from lifespan experiments are mainly analysed in the original study, and data are not collected and stored together. Meta-analyses are mainly limited to either sufficiently large subsets of survival data acquired under identical conditions or the application of methods accounting for varying additional factors. The published meta-analyses of survival data have mostly assessed CR. For example, reportedly, CR significantly extends lifespan, and the proportion of protein intake is more important for lifespan extension than the degree of CR. No study has demonstrated whether CR, genetic manipulation, or pharmaceutical administration is superior at extending lifespan and delaying ageing.
Here, we attempted to resolve this question by conducting a comprehensive and comparative meta-analysis of the effect patterns of these different interventions and their corresponding mechanisms via survival curves. We have focused our analyses on Caenorhabditis elegans and Drosophila, powerful model systems that are widely used in ageing research. We developed an algorithm that enabled us to combine multiple strains of these species from a large number of studies and to extract general trends from relevant results.
Our study indicated that CR and genetic manipulations are effective ways in delaying senescence. The effect pattern of CR is superior to that of genetic manipulation in Caenorhabditis elegans but similar to that of genetic manipulation in Drosophila. Genetic manipulation in mammals faces many problems and risks, and CR, including changes in diet composition, time-restricted feeding, or CR mimetics, could be a more feasible approach for humans. These considerations and our results support CR as a feasible and effective anti-ageing intervention.