The problem of Caloric Restriction as an intervention to extend healthspan

Humanity has been obsessed with the idea of ‘extending life’ for thousands of years. Philosopher’s stones, fountains of youth, spells, and magic… despite the claims and promises nothing seemed to work. That is until we decided to approach the problem with a scientific mind. Almost one hundred years ago, in the 1930s, scientist described that a 20–40% reduction in food intake could extend the life of laboratory rats by up to 50% (McCay, C. M. and Mary F. Crowell, 1934). This intervention, termed caloric restriction (CR), is defined as a reduction in caloric intake without reaching malnutrition. The beneficial effects of CR on health and lifespan have been reproduced in pretty much every organism it has been tested on, making CR the most robust anti-aging intervention as of today (Table 1).

Table 1: Effects of dietary restriction on model organisms, adapted from Fontana et al, 2010

Importantly, although the effects on primates lifespan are unclear, the health benefits of CR seem to hold true.

CR Rhesus monkeys are protected from multiple age-related conditions and this is also reflected in the way they look (Figure 1).

Figure 1: 27.6-year-old control animal (A-B) vs age-matched CR animal (C-D) from a longitudinal adult-onset CR study (Colman et al., 2009).

Thanks to many years of research, we now know much more about the biology behind CR. For example, we know it is not the number of calories but the type of nutrients consumed, particularly the amount of proteins, what mediates the beneficial effects of this dietary intervention. For this reason, the appropriate term to be used is dietary restriction (DR). However, if this intervention is so robust, why don’t we all follow that diet? Well, it turns out that to reach a DR-state you should reduce your dietary intake by about 30%, and this is extremely hard. Even if you tried, chances are you will not be able to stick to that kind of diet for a long time. Moreover, DR also comes with a couple of negative side effects, such as delayed wound healing.

Concluding: Developing an intervention that would allow us to reap the benefits of DR without food-torturing us in the process would be an excellent way to treat or even prevent the conditions associated with old age.