Dietary restriction by avoiding malnutrition robustly extends the Lifespan from yeast to rodents. DR is the only regimen that extends the Lifespan and healthspan in a spectrum of organisms including yeast, mice and nonhuman primates [Colman et al. 2009; Mattison et al. 2012; Weindruch et al. 1986].
Reducing the food consumption 25-60% without malnutrition extends the Lifespan of rodents up to 50% [Weindruch et al. 1986] and delays the onset of age-related maladies [Colman et al. 2009; Koubova & Guarante, 2003].
In mice and rats, DR can extend longevity by up to 50%, delay physiological Aging and postpone or diminish the morbidity of most age-related diseases .
DR elicits major metabolic reprogramming toward efficient fuel utilization and reduction in oxidative damage to macromolecules [Anderson & Weindruch, 2012; Sohal and Weindruch, 1996].
DR triggers global reprogramming of mitochondrial protein acetylome [Herbert et al. 2012].
A restricted diet lowers IGF1 levels, favors Apoptosis over cell proliferation and slows down tumor progression. Restoring normal ad libitum IGF1 levels in mice under DR abrogates the protective effect of DR on neoplastic progression .
Mice undergoing 40% DR from the age of 3 month exhibit a lower levels of Telomere shortening rate than those fed a normal diet. DR mice have therefore lower rates of chromosome anomalies. Mice that fed a lower caloric diet have a reduced incidence of Cancer as well as a lower incidence of other age-related illnesses such as osteoporosis, greater glucose uptake or improvements in motor coordination .
Mice engineered to produce produce more Telomerase (the protein that lengthens Telomeres and protects chromosomes enjoy an better health and live up to 20% longer. The significant increase in longevity is likely due to the protective effect against Cancer produced by DR as the Cancer incidence is 40% lower when compared with mice that overproduce Telomerase and have a normal diet [http://www.biocompare.com/life-science-news/129511-caloric-restriction-has-a-protective-effect-on-chromosomes/; http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053760] 23349740].
In long-lived wild derived Strains of mice the benefits of DR are less clear .
Whether DR also prolongs Lifespan in primates is questionable.
First studies in rhesus monkeys indicate a longer Lifespan, due to an overall reduced mortality . However this was only true if censorship duo to non-age-related diseases was applied. Another study done by National Institute of Health (NIA) did not revealed any average Lifespan benefit from a 30% DR. DR improves some test results, but only in monkeys put on the diet when they were old. Still an effect on Maximum Lifespan remains unknown [http://www.nytimes.com/2012/08/30/science/low-calorie-diet-doesnt-prolong-life-study-of-monkeys-finds.html?_r=1; http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11432.html].
The Wisconsin monkeys got a much higher sucrose content in their food than the NIA animals. Wisconsin control animals could eat as much as they like, while the NIA control were given a set amount of food.
When done probably DR appears to confer health-benefits, such as lowering the risk of heart disease. People on DR have hearts that function more like those found in people two decades younger.
Still a severe restricted diet can lead to low Testosterone levels and problems with maintaining bone density in male individuals [http://online.wsj.com/article/SB10000872396390444772804577619394017185860.html].
Colman, R.J., Anderson, R.M., Johnson, S.C., Kastman, E.K., Kosmatka, K.J., Beasley, T.M., Allison, D.B., Cruzen, C., Simmons, H.A., Kemnitz, J.W., and Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204.
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., et al. (2012). Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321.
Weindruch, R., Walford, R.L., Fligiel, S., and Guthrie, D. (1986). The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116, 641–654.
Anderson, R.M., and Weindruch, R. (2012). The caloric restriction paradigm: implications for healthy human aging. Am. J. Hum. Biol. 24, 101–106.
Koubova, J., and Guarente, L. (2003). How does calorie restriction work? Genes Dev. 17, 313–321.
Sohal, R.S., and Weindruch, R. (1996). Oxidative stress, caloric restriction, and aging. Science 273, 59–63.