Fasting, Aging Monkeys, and Brain Tumors

Fasting (or more specifically, caloric restriction or CR) is often mentioned as a way to extend life- and healthspan. By reducing the caloric intake by 10 – 40%, rodents, fruit flies, and tiny roundworms have been shown to live significantly longer. Aha, have we found the key to longer and healthier human lives? Maybe that’s a conceptual leap too far.

Two male rhesus monkeys (27 years of age), one on a CR diet (left) and one on a regular diet (right).
(Source: National Institute on Aging)

Primate studies are not unequivocal. Some have shown life extension, but a recent study from the National Institute on Aging (NIA) does not. It does, however, show several health effects. There were two groups of rhesus monkeys (actually more because you need controls, of course).

Anyway, the old-onset monkeys were put on a CR diet when they already reached the ripe and mature age of 16 – 23 years (average lifespan in captivity is about 27 years, with exceptions up to 40). The CR monkeys did not live longer than their control counterparts. But, they did show a lower weight (especially in the males), lower triglycerides, and lower cholesterol and glucose in males.

A little less than half of the animals from the second group, the young-onset CR monkeys, is still alive, so conclusions here are tentative. At the moment, there’s no significant effect on lifespan and estimates do not predict one. Furthermore, these young-onset CR monkeys showed less of the expected benefits from their diet than those that started at a more advanced age. The males had a somewhat lower level of triglycerides. The young starters, however, did show an improved immune response and a lower incidence of cancer.

These findings contrast with a previous study by the Wisconsin National Primate Research Center (WNPRS), which did find a positive effect on the lifespan on CR monkeys. Whence the difference? Some factors the authors from the NIA study mention:

• Different diets. The NIA diet was more natural, whereas the WNPRS diet was purified (meaning that each ingredient provides a specific nutrient. The nutrient sources also differed. Further, the NIA study used only one diet for both CR and control monkeys (of course in larger quantity for the control animals).

• Regulation. The portioning of the NIA diet was more regulated than the WNPRS one in which the monkeys were fed ad libitum.

• Background. The NIA monkeys had a genetically more diverse background coming from both China and India. Their WNPRS cousins came exclusively from India.

• Age of onset. The NIA study put both young and mature rhesus monkeys on a diet, the WNPRS study only adults.

So, where does this leave us? Well, caloric restriction might have an effect on primate (including human) lifespan, but this is far from certain. There appear to be many contributing factors that should be investigated further. There seem to be some health benefits associated with CR in primates, but again, more research is needed.

Brain tumors then.

Say what? What do brain tumors and fasting have to do with each other? Well, a new study found that fasting improves the response of brain tumors to chemo- and radiotherapy. By subjecting mice with brain tumors to a 48-hour period of starvation, it was found that, as suggested by earlier research, their tumors were more sensitive to chemo- and radiotherapy, leading to extended survival of the rodents. Similar results were found in in vitro tests on mouse, rat and human brain tumor cell lines.

What happens here? The response to short-term starvation (or STS) is quite complicated, but one of the things that happens, is that the levels of glucose and IGF-1 (insulin-like growth factor 1) drop. This leads to the activation of cellular protection mechanisms in normal cells, but not in tumor ones, which are more self-sufficient. Furthermore, a reduction in glucose and IGF-1 results in a different stress response in normal and cancer cells. So, STS does not only lead to protection of regular cells, it also makes tumor cells more vulnerable to chemo- and radiotherapy.

Keep in mind though that STS is not the same as CR. The former is a 48 hour period of no food, whereas the latter is a lifetime of less food. (However, CR might also lead to lower glucose and IGF-1 levels). And now, the search is on for methods to mimic STS and CR.

All this has made me hungry. Damn.

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Mattison, J.A., Roth, G.S., Beasley, T.M., Tilmont, E.M., Handy, A.M., Herbert, R.L., Longo, D.L., Allison, D.B., Young, J.E., Bryant, M., Barnard, D., Ward, W.F., Qi, W., Ingram, D.K., & de Cabo, R. (2012). Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature, 489, 318-321 DOI: 10.1038/nature11432

Safdie, F., Brandhorst, S., Wei, M., Wang, W., Lee, C., Hwang, S., Conti, P.S., Chen, T.C., & Longo, V.D. (2012). Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy. PLOS ONE, 7 (9) DOI: 10.1371/journal.pone.0044603