While studies in animals provide good evidence for the relationship of CR and longetivity, studies in humans are less certain. To date, there are few studies that have examined this relationhip in humans, due to ehtical, as well as methodological reasons. An important point to note is that even if the results do prove meaningful in human terms, it remains to be seen whether people will actually do anything about it.

Differences between energy and nutrients:
Just because a diet is low in energy (calories), doesn't mean it has to be low in nutrients. A nutrient dense diet can provide all of the nutrients you need while restircting calories. This is the a MAJOR point of this relationahip: evidence pointing towards benefits in CR diets mean that the diets must be low in calories yet HIGH in nutrients. Consider malnourished populations whose energy is low not by choice, but by the result of poverty. In this situation, the person is lacking in protein and micronutrients -- associated with short stature, malnutrition, and impaired immune functions. The kind of CR diet suggested in this entry does not promote malnutiriotn, but rather reduces energy while mainting micronutrients necessary for the body to thrive.

Nutrient dense vs. nutrient low diets with equal caloric intakes:
Nutrient Dense (%RDI

Breakfast: 1 cup total, ˝ cup 2% milk, 1 cup blueberries
Lunch: 1 cup raw broccoli, I cup raw carrots, ˝ cup tuna salad, 1 medium piece mulit-grain toast
Snacks: 8 oz. plain yogurt, 1 oz. almonds
Dinner: 2 eggs, ˝ cup tomato, 1 cup spinach, ˝ cup mushrooms

Select Micro/Macro-nutrients:
Energy: 1324 (60%)
Protein: 69 (137%)
Saturated Fat: 13
Unsaturated Fat: 36
Fiber (gm): 24 (95%)
Vit A(RE): 4895 (699%)
Iron (mg): 30 (166%)
Calc (mg): 1190 (119%)
Vit E (α-TE): 41 (276%)
Folate (mcg): 737 (184%)
Vt C (mg): 226 (302%)

Nutrient Low (%RDI):

Breakfast: 1 poptart
Lunch: 1 Arby’s roast beef sandwich, I bag pot. Chips, I small (16 oz. ) coke
Snacks: milkshake (10 oz)
Dinner: spaghetti and meatball frozen meal (12.5 oz)
Energy: 1304 (59%)
Protein: 42 (84%)
Saturated Fat: 13
Unsaturated Fat: 22
Fiber: 8 (33%)
Vit A: 377.7 (54%)
Iron: 8.9 (49%)
Calc: 310 (31%)
Vit E: 3.8 (25%)
Folate: 120 (30%)
Vt C: 44 (58%)

Tips:
avoid simple sugars and flours
Eat both green leafy (salad) and other vegetables
Carefully select your protein and fat sources
Make sure your protein intake is sufficient, but not overly abundant
Make sure your proteins are complete and balanced
Most animal proteins are complete and well-balanced
Non-animal proteins can be balanced by combining different food families
Select monounsaturated fats, avoid saturated fats, and consume some Omega-3 fats

Cautions and Hazards!
Along with all its demonstrated and potential benefits, calorie restriction may result in a range of negative side effects.
Those interested in the calorie-restricted lifestyle should be aware of the following potential issues:

anemia -- noted by at least one Society member. Several human and animal studies suggest that people practicing CR may experience anemia, even if iron intake is adequate by RDA standards. This may be aggravated by low iron intake if red meat consumption is curtailed as part of one's CR program. Monitoring iron status with a ferritin test is recommended.
"negative" appearance changes -- CR-induced weight loss can affect the appearance ofthose who pursue it. In the overweight, these changes may be perceived positively -- but in others, negative perceptions may arise.
bone health -- while evidence suggests that CR may support long-term skeletal health, weight loss is often accompanied by reduced bone mass, which may place you at risk of fracture. Work with your physician to monitor your bone mass and markers of resorption.
risk of choking -- potentially exacerbated via CR-induced, eat-quicky psychology.

cold sensitivity -- reduced body fat and decreased body temperature can make practitioners more sensitive to cold temperatures, while perhaps decreasing their sensitivity to extreme heat. Reduced fat can also make one's skin more sensitive to very warm or hot surfaces or liquids, such as hot tap water. This may put you at greater risk in case of unexpected, prolonged cold exposure -- such as after a car failure on the highway in winter.
children, adolescents, and young adults (under approx 21) should be advised against starting CR. Physical growth may be impaired by calorie restriction, as observed in lab animals. In addition, mental development and physical changes to the brain take place in late adolescence and early adulthood that could be negatively affected by calorie restriction. For this group, the best advice is to follow a healthy, normal (non-CR) diet until reaching early twenties.
loss of "cushioning" -- discomfort sitting on hard surfaces, etc., due to reduced body fat. Similarly, body tissues will be less protected from impact, leading to greater risk of damage to underlying tissues - such as bone or soft tissues.

depression and/or "emotional deadening" -- although anecdotal, it is reported often enough to make noteworthy. People report that when their energy intake/BMI drops too low, they have difficulty functioning properly and things seem negative and/or meaningless. They state that upon increasing calorie intake/BMI, things improve.
reduced energy reserves (due to less body fat) -- being unexpectedly stuck on a boat, locked in a room or lost in a wilderness are all scenarios where energy reserves may be important.

Evidence:
There is limited human studies in theis relationsip. The few observational studies that exisit often involve cultures that typical eat a diet low in calories -- not nessarily restriction. One of the most well known involves a gorup of centenarians

Animal Studies:

Mechanism:
In animals on a full diet, aging appears to alter the activity of a series of genes -- activating some and turning others off -- that affect the ability of the hardest working cells in the body to carry out their functions and remain healthy over time. Caloric restriction, among other things, inhibited the genes involved in cell death and that prompt inflammation, suggesting that the heart cells of animals on a restricted calorie diet are healthier overall.
Our present work in rodents involves testing the possibility that CR acts by reducing oxidative stress in postmitotic tissues. In 1998, a collaboration began with Dr. Tomas Prolla using oligonucleotide microarrays to conduct the first gene expression profiling studies in gerontology. Data from these studies strengthen the idea that CR may slow aging by reducing free radical damage to tissues. Whether this mechanism is operative in opposing late-life cancers is worthy of expanded exploration.

Good article:

Atwood, C.S., Barzilai, N., Bowen, R.L., Brown-Borg, H.M., Jarrard, D.F., Fu, V.X., Heilbronn, L.K., Ingram, D.K., Ravussin, E., Schwartz, R.S., Weindruch, R. (2003). Pennington Scientific Symposium on Mechanisms and Retardation of Aging. Experimental Gerontology 38(10), 1217-1226.

Lee, C.K., Allison, D.B., Brand, J., Weindruch, R., Prolla, T.A. (2002). Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc. Natl. Acad. Sci. U.S.A, 99, 14988-14993.

Kayo, T., Allison, D.B., Weindruch, R., Prolla, T.A. (2001). Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc. Natl. Acad. Sci. U.S.A., 98, 5093-5098.

Weindruch, R., Keenan, K.P., Fernandes, G., Feuers, R.J., Floyd, R.A., Halter, J.B., Ramsey, J.J., Richardson, A.G., Spindler, S.R. (2001). Caloric restriction mimetics: Metabolic interventions. J. Gerontol. Biol. Sci., 56A, 20-33.

Lopez, M.E., Van Zeeland, N.L., Dahl, R. D., Weindruch, R., and Aiken, J.M. (2000). Cellular phenotypes of age-associated skeletal muscle mitochondrial abnormalities in rhesus monkeys. Mutation Research, 452,123-138.

Ramsey, J.J., Colman, R.J., Binkley, N.C., Christensen, J.D., Gresl, T.A., Kemnitz, J.W. and Weindruch, R. (2000). Dietary restriction and aging in rhesus monkeys: The University of Wisconsin Study. Exp. Gerontol., 35, 1131-1149.

Hall, D.M., Oberley, T.D., Moseley, P.M., Oberley, L.W., Weindruch, R., Kregel, K.C. (2000). Caloric restriction improves thermotolerance and reduces hyperthermia-induced cellular damage in old rats. FASEB J., 14, 78-86.

Zainal, T.A., Oberley, T.D., Allison, D.B., Szweda, L.I., Weindruch, R. (2000). Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J., 14, 1825-1836.

Lee, C.K., Weindruch, R., & Prolla, T.A. (2000). Gene expression profile of the aging brain in mice. Nat. Genet., 25, 294-297.

Ramsey, J.J., Harper, M.E., & Weindruch, R. (2000). Restriction of energy intake, energy expenditure, and aging. Free Radic. Biol. Med., 29, 946-968.

Pugh, T.D., Oberley, T.D., Weindruch, R. (1999). Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. Cancer Res., 59:1642-1648..

Lee, C.K., Klopp, R.G., Weindruch, R., & Prolla, T.A. (1999). Gene expression profile of aging and its retardation by caloric restriction. Science, 285, 1390-1393.

Ripple, M.O., Henry, W.F., Schwarze, S.R., Wilding, G., & Weindruch, R. (1999). Effect of antioxidants on androgen-induced AP-1 and NF-kappa B DNA-binding activity in prostate carcinoma cells. J. Natl. Cancer Inst., 91, 1227-1232.

Weindruch, R. and Sohal, R.S. (1997). Caloric intake and aging. New Engl. J. Med., 337, 986-994.

Weindruch, R. (1996). Caloric restriction and aging. Scientific American, 1, 46- 52.

Sohal, R.S., Weindruch, R. (1996). Oxidative stress, caloric restriction, and aging. Science, 273, 59-63.

Weindruch, R. and Walford, R.L. (1988). The retardation of aging and disease by dietary restriction C.C. Thomas, Springfield IL.