Get back–calorie restriction: Dr. Masoro’s legacy

After the initial discovery by MaCay and colleagues, which showed that reduced food intake extended the lifespan in rats, many aging researchers used calorie restriction (CR) as an experimental paradigm to seek the underlying mechanisms of aging and anti-aging actions of CR. Among those many researchers, one of the most intensive and systematical studies was carried out by Dr. Edward Masoro and his colleagues. Dr. Masoro’s approach with a strict animal maintenance protocol in a barrier facility along with using a defined semisynthetic diet allowed him to yield a large amount of data and very important information for the advancement of current aging research to areas such as reduced GH/IGF-1 actions, suppression of mTOR signaling, reduced senescent cell accumulation, enhanced insulin sensitivity and signaling, and others (Sirt1 and hormesis), etc. The interventions of a single mechanism/pathway have demonstrated an exciting and promising outcome for the translational aspect to humans. However, CR is still considered the most effective intervention of aging. The mammalian aging process seems to be far more complex than our initial prediction, and the anti-aging effects shown by CR require synergistic alterations of multiple mechanisms/pathways. Therefore, it may be time for us to get back and re-visit Dr. Masoro’s legacy by further examining the complexity of mechanisms of aging and the effects of CR. These further experiments are necessary to validate the successful implementation of CR to human aging (including lifespan, healthspan, and various age-related diseases) because of its diversity of genetic backgrounds, dietary compositions, lifestyle, and other factors that are different from the experimental animals in well-defined laboratory conditions.