11.16: Nutrition and Maximum Longevity

Animals in laboratories are often provided with food at all times. The food provides contains a balance of nutrients. The animals can eat as much as they want any time they want. Animals able to eat freely in this way are said to be fed ad libitum (AL). In other cases, the food provided and the times it is provided are restricted. These animals are undergoing dietary restriction (DR).

In 1937, McCay reported that DR rats that were provided 33 percent less food than the amount eaten by AL rats had significant increases in meal longevity (ML) and maximum longevity (XL). Since then, DR has resulted in increases in ML and in XL for many types of animals including roundworms, spiders, insects, and mice.

Attempts to identify the means by which DR increases ML and XL revealed that the essential factor is the reduction in calories eaten by the animals. As long as the animals are fed balanced diets, only the number of calories eaten affects both the ML and the XL consistently. The types of nutrients in the diet and the times of eating do not cause the increases in ML and XL. Therefore, dietary restriction is now called caloric restriction (CR). CR animals have undernutrition without having deficiencies in any particular nutrient (e.g., protein, lipids, minerals, vitamins). Though extreme CR (e.g., 60 percent CR) leads to unhealthy underweight conditions, undergoing reasonable CR (e.g., 30 percent CR) and being underweight from malnutrition are different entities. (Suggestion 251.02.05)

Effects from CR

Though many other treatments can increase ML in animals and in humans, CR is the only means known to increase the XL of animals. Therefore, scientists believe that CR actually slows fundamental aging processes. Research with CR in monkeys and in humans is underway. CR has been shown to increase ML in monkeys.

In rats and mice (i.e., rodents), CR increases ML and XL by 25 percent to 30 percent. Animals undergoing CR also develop fewer diseases, develop diseases at later ages, and develop milder forms of disease. CR has different degrees of effect on ML, XL, and diseases depending upon when CR begins, how severe it is, and how long it lasts. CR has detrimental effects if it begins during early development, but after that, the earlier it begins, the greater the effect. Also, the longer CR lasts, the greater the effect.

CR causes many beneficial effects in the animals in which it has been tested. These effects may contribute to the increases in ML and XL and the reductions in diseases. Most of the effects relate to the causes of aging proposed in the theories of aging (see Chapter 2). However, the mechanisms by which CR increases ML and XL and reduces disease are not known.

Specific benefits from CR include slowing the age-related increases in the following: free radical production; free radical damage; protein cross-links and protein glycation; lipofuscin formation; mitochondrial damage; blood pressure; blood LDLs; blood triglycerides; blood glucose; blood insulin; obesity; diabetes mellitus; percent body fat (usually); IL-6; kidney disease; and cancers. CR slows or delays the age-related declines in HDLs; number of muscle cells; rate of protein synthesis; DNA repair; insulin sensitivity; certain hormones (e.g., melatonin, DHEA); immune function (usually); IL-2; physical activity; and general health (e.g., skin, cardiovascular, kidneys).

Exercise produces many of these effects. Scientists have shown that CR does not increase ML and reduce diseases in the same ways that exercise produces these effects. Though both CR and exercise increase ML and reduce diseases, their effects are independent, not synergistic. The effect on ML in animals having both CR and plenty of exercise equals the sum of effects on ML seen in sedentary animals with only CR and the effects seen in AL animals with plenty of exercise. Finally, exercise does not affect XL.

How animal studies with CR can be applied to human aging is still being determined. The effects of CR on humans are still unknown. Unlike animals, humans who subsist on diets containing few kilocalories or low protein, such as people living in poor and overcrowded areas, have shorter mean longevities. No individuals like that ever exceed the maximum human longevity of 120 years. Of course, these CR people do not eat carefully compounded and analyzed laboratory feeds and do not live in the controlled environment of a laboratory, receiving inoculations, continuous monitoring, and ongoing professional care. Could humans living most of their lives in such conditions and eating limited amounts of only certain selected types and quantities of food at specified times every day have greater maximum longevity? Would an increase in maximum longevity be worth the effort? How much could longevity be increased by CR among people living more conventional lifestyles? If the mechanisms by which CR works are discovered, will it be possible to produce those mechanisms in humans without requiring them to undergo CR? Future research may eventually answer these questions.

For the Wikipedia on-line encyclopedia site on caloric restriction, go to http://en.Wikipedia.org/wiki/Caloric_restriction .

For the NIA web page on caloric restriction, go to https://www.nia.nih.gov/site-search/caloric restriction .

For the Caloric Restriction Society web site, go to http://www.crsociety.org/ .