Caloric restriction slows immune aging

The link between caloric restriction and longevity may be mediated by reduced susceptibility to disease, researchers report this week in the Proceedings of the National Academy of Sciences. The scientists found that calorie-restricted older adult rhesus monkeys have at least 30% more na￯ve T cells than controls.

"This is the first study that shows caloric restriction maintains na￯ve T cells in primates," study co-author Ilhem Messaoudi of the Oregon National Research Primate Center told The Scientist.The link between calorie restriction and na￯ve T cells was previously demonstrated in mice by Richard Miller and his team at the University of Michigan.

"Some people said there's something special about short-lived animals and that this wouldn't work in humans," Miller, who was not involved in the monkey study, told The Scientist. "This is one of the very best pieces of evidence that show those doubters may be wrong. If it works in something as long-lived as a rhesus monkey, then there's reason to hope that caloric restriction principles can work in people as well."

The research team, led by Janko Nikolich-Zugich at the Oregon National Research Primate Center, fed 13 rhesus monkeys 30% fewer calories than a control group of 29 monkeys for 13 to 18 years, with caloric restriction starting at three to five years of age, which is around puberty for monkeys. The experimental and control animals received the same levels of vitamins and minerals.

Research at the Wisconsin National Primate Research Center had shown that monkeys restricted in calories for two to four years showed minimal differences from controls in terms of na￯ve T cells. But that research may have been too short-term, said Nicklich-Zugich, explaining that "caloric restriction is a form of stress, and the organism needs to adapt, so fluctuation [during the early years] is very possible." For his group of monkeys, the earliest point of sampling was after 10 years of caloric restriction.

Using peripheral blood collected at four points over 42 months, the researchers calibrated for white blood cells, lymphocytes, and neutrophils and used flow cytometry to distinguish na￯ve and memory T cells. The stained samples illustrated that control monkeys had a lower percentage of na￯ve T cells (20-25%) than the calorie-restricted monkeys (30-35%).

This is a "fairly striking difference," said Richard Weindruch of the University of Wisconsin, who was not involved in the study. "This is the strongest evidence to date that in a primate species, caloric restriction is able to slow down immunological aging."

What the T cell differences mean in terms of lifespan remains an open question. "It's not clear if improvements in immune function would increase maximum lifespan as well as reduce morbidity," Susan Roberts, senior scientist at Tufts University's Jean Mayer USDA Human Nutrition Research Center on Aging, told The Scientist in an email. Roberts was not involved in the current study.

According to Messaoudi, the team will follow the monkeys through the end of life to address this issue. But Miller would like to see another focus.

"Whether diet extends lifespan may be the wrong question to be asking," he told The Scientist, pointing out that the cause of death in monkeys may have no link to aging. "What I'd love to see is how caloric restriction affects hearing, eyesight, muscle strength, wound-healing...If caloric restriction slows down the change in three or four of these systems, then [there is] a strong case that aging is being slowed regardless of how the lifespan data comes out."

The new finding maps onto recent studies proposing mechanisms that underlie caloric restriction and aging, including temperature effects and how resveratrol may influence the same metabolic pathways as caloric restriction.

Cathy Tran
ctran@the-scientist.com

Links within this article:

P. McCarthy, "Scientists Finding Evidence Of Caloric Restriction's Benefits," The Scientist, May 26, 1997
http://www.the-scientist.com/article/display/17566

J. Olshansky et al, "In pursuit of the longevity dividend," The Scientist, March 2006
http://www.the-scientist.com/article/display/23191

Proceedings of the National Academy of Sciences
http://www.pnas.org

M. Anderson, "Sir2: Scrambling for Answers,"The Scientist, December 6, 2004
http://www.the-scientist.com/article/display/15122

Oregon National Research Primate Center
http://onprc.ohsu.edu

Richard Miller
http://www.pathology.med.umich.edu/faculty/Miller/index.html

Janko Nikolich-Zugich
http://www.ohsu.edu/vgti/nikolich.htm

Wisconsin National Primate Research Center
http://www.primate.wisc.edu

J. Roberts, "Flow Cytometry," The Scientist, May 5, 2003
http://www.the-scientist.com/article/display/13756

Richard Weindruch
http://aging.wisc.edu/research/affil.php?Ident=67

Susan Roberts
http://hnrc.tufts.edu/scientists/people/sroberts.php

C. Choi, "Cooler mice live longer,"The Scientist, November 2, 2006
http://www.the-scientist.com/news/display/27374'

Baur JA et. al., "Resveratrol improves health and survival of mice on a high-calorie diet," Nature. 2006 Nov 16;444(7117):337-42. Epub 2006 Nov 1.
http://www.the-scientist.com/pubmed/17086191