Eat Less to Live Longer?
Yeast, worms, flies and rodents all show a marked physical response when food supplies drop off. Their cells slow development, halt reproduction, reduce their metabolic rate, and sometimes enter a hibernation-like state. As early as the 1930s, scientists like Cornell University veterinary nutritionist Clive McCay discovered that putting male rats on a calorie-restricted diet extended their lifespan by up to 75 percent. (16)
More recent studies published in the New England Journal of Medicine and elsewhere show rodents on calorie-restricted diets not only live longer, but experience cancer, cataracts, diabetes and hypertension much later in life than their counterparts who are eating at will.
"However long you live, you will probably have some period of illness and disability, on average, between three and five years," Harman says. The difference is that with lifespan extension, this period will occur much later. "That's exactly what we see in these animals in which we restrict calories by 25 to 30 percent. They develop the same diseases, but later [than their counterparts on regular diets]." (17)
Restricting calories practically prevents the development of autoimmune diseases in certain strains of mice. For example, when mice susceptible to a lupus-like disease are fed at will, they contract the disease and usually die around 12 months of age. The mice on calorie-restricted diets appear less likely to contract the disease and live to about 20 months. (18)
Perhaps most dramatic are the caloric restriction studies now underway in rhesus monkeys. At the Wisconsin National Primate Research Center, older rhesus monkeys on normal diets are frail and wrinkled, barely energetic enough to grab a piece of fruit, while their thin and energetic peers on calorie-restricted diets parade around their cages. (19)
Dr. Don Ingram, who recently left the NIH in Maryland after 26 years to return to his native Louisiana, has been a leader in the study of calorie restriction.
In a recent interview with Pennington Biomedical Research Center (PBRC) in Baton Rouge, where he now is a faculty member, Ingram said: "If you're going to stop growing and reproducing, you better have a way to survive, and these organisms have a number of genes that, when stimulated by low energy (food) intake, lead to a cascade of responses that eventually result in slowing many aging processes, and thus produce subsequently greater health and longer life." (20)
PBRC is working with grants from the NIA to study these effects in humans. (21)
Ingram is working to develop a compound that would mimic in humans the effects of eating a third less calories because, as any dieter knows, sticking to a long-term diet, particularly such a severe one, is unrealistic for most people. (22)
Reducing Cell Damage Slows Aging
Aside from a severe calorie-restricted diet or a simulated one, scientists are exploring other interventions to slow the aging process in humans, honing in on how to reduce cell damage due to compounds called "oxygen free radicals." These compounds are mainly generated as a byproduct of normal cell processes that produce energy. They act like powerful explosives, damaging nearby molecules. As cells age, they become increasingly unable to use oxygen and fuel efficiently to generate energy. This effect is known as "oxidative stress." There is much evidence that oxidative stress plays an important role in causing age-related diseases like cancer and Alzheimer's.
KLRI, in collaboration with Dr. L. Jackson Roberts at the Vanderbilt University College of Medicine, began a study in August 2006 to explore differences in how younger and older men and women react to acute oxidative stress produced by temporarily blocking arterial blood flow to the forearm. Through this study, they hope to develop a way to test potential interventions, like antioxidants, nutrients, and exercise, for their impact on oxidative stress. (23)
The Right Nutrition and Exercise Can Help
We have known for years that exercise can keep people stronger longer, but a recent study by the Group Health Center for Health Studies in Seattle suggests regular exercise may also stave off mental decline. (24)
The study shows that people in poor physical shape are more likely to develop dementia. "The two processes are intimately connected," Dr. Eric Larson, a co-author of the study, recently told the New York Times. "People more likely to develop dementia show early signs of physical function decline, and people, especially in old age, will develop decline in physical function as a result of dementia that may be too mild to be detected."
On the dietary side, KLRI is studying the effects of high doses of omega-3 polyunsaturated fatty acids, the good fats found in fish and other foods. Preliminary findings in a small study are about to be published in a prominent medical journal that show healthy men and women over 60 years of age taking these supplements showed significant improvement in mental tests and improvements in their body's use of insulin after just eight weeks. Follow-up studies are planned that would combine the supplements with exercise and other interventions. (25)
Resveratrol, a compound found naturally in red wine and thought to have anti-aging properties, will be studied by KLRI in collaboration with a prominent neuroscience research group in Phoenix. They will explore how the compound may affect insulin sensitivity in diabetics over 55 years of age, (26) and its effects on brain aging, mental function, body composition and muscle function.
Unlocking the Mysteries of Hormones
The NIA is conducting trials on whether estrogen therapy protects older women from mental decline, with completion expected by December 2008. (27)
KLRI is sponsoring a long-term research project with nine academic research centers on the potential power of estrogen therapy to ward off heart disease in women who have recently entered menopause called Kronos Early Estrogen Prevention Study (KEEPS).
KEEPS is looking at whether estrogen therapy, given at low doses to recently menopausal women, protects them against hardening of the arteries. It is also studying whether different therapy delivery systems, i.e. the administration of a skin (transdermal) patch versus an oral dose, makes a difference in the outcomes.
On another hormone front, in partnership with a research team at Boston University, KLRI is studying testosterone in older men. As men age, their testosterone levels naturally decline. The Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) study is designed to assess testosterone effects on hardening of the arteries, as well as how beneficial testosterone therapy can be in maintaining bone density, muscle mass, energy and sex drive.
A study recently published in the Archives of Internal Medicine suggests that men with high testosterone levels may also live longer than those with low levels. (28) "A lot of men have gotten the idea that testosterone is the fountain of youth," says Harman. "This is clearly not the case, but it seems to be of some help for older men with low levels," he says. (29)
Some Cells Take on Many Roles
KLRI is developing a study to explore the impact of the injection of umbilical cord blood stem cells on the immune system of diabetics. Type 1 diabetes occurs due to destruction of the insulin secreting cells of the pancreas by the patient's own immune cells (autoimmunity). A fraction of cells found in the umbilical cord blood of newborn infants have the ability to develop into almost any type of cell, and shows promise in regulating immune function and perhaps becoming insulin-secreting cells as well. (30)
This type of approach, replacing cells that have lost normal function with new young cells, has promise for rejuvenating aging bodies by replacing worn-out cells.
16. Sagecrossroads.net [Internet]. Washington DC: Alliance for Aging Research: What's Next for Longevity Research? Mooney C. [2003 May 19; cited 2007 March 14]. Available from: http://www.sagecrossroads.net/Default.aspx?tabid=28&newsType=ArticleView&articleId=12.
17. Harman, SM [phone interview 2006 Dec 20].
18. Weindruch R, Sohal R. Caloric Intake and Aging. N Engl J Med 1997. 337: 986-994
19. Newyorktimes.com [Internet]. New York: New York Times Company: One for the Ages: A Prescription That May Extend Life. Mason M. [2006 Oct 31; cited 2007 Jan 22]. Available from: http://www.nytimes.com/2006/10/31/health/nutrition/31agin.html?ex=1169614800&en=07b41ea1fbc24e53&ei=5070.
20. Mimicking a Good Thing. Nutrition Matters. Pennington Biomedical Research Center and Foundation. Baton Rouge. Fall 2006. 1.
21. Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy, Pennington Biomedical Research Center [Internet.] Baton Rouge; [2003; cited 2007 Jan 21]. Available from: http://calerie.pbrc.edu/.
22. Pennington Biomedical Research Center [Internet.] Baton Rouge; [2006 Nov 30; cited 2007 Jan 21]. Available from: http://www.pbrc.edu/News/News_Story.asp?id=68.
23. Harman, SM. KLRI's Research Agenda: Today and Where to Next? Longevity Kronicle. 2006. 6:15. 2-3.
24. Newyorktimes.com [Internet.] New York: New York Tines Company: Aging: Hit the Health Club: Offset Dementia's Onset. Bakalar N. [2006 May 23, cited 2007 Jan 26]. Available at: http://www.nytimes.com/2006/05/23/health/23agin.html?ei=5070&en=ed4e56d3330ecbc1&ex=1169960400&adxnnl=1&adxnnlx=1169815284-Ib9daNn5B6nPaw9kBeZO/g.
25. Harman, SM. KLRI's Research Agenda: Today and Where to Next? Longevity Kronicle. 2006. 6:15. 2-3.
26. Harman, SM [phone interview 2006 Dec 20].
27. Clinicaltrials.gov [Internet]. Washington: U.S. National Institutes of Health; [updated 2006 Nov 11; cited 2007 Jan 22]. Available from: http://clinicaltrials.gov/show/NCT00097058.
28. Harman, SM. KLRI's Research Agenda: Today and Where to Next? Longevity Kronicle; 2006. 6(15), 2-3.
29. Harman, SM [phone interview 2006 Dec 20].
30. Ibid.
