"Caloric Restriction and Restrictive Diets: Interventions that Target the Biology of Aging," as the latest special issue of The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences is titled, contains a collection of articles with new research on a proven method for increasing longevity in many organisms -- including the results of the first-ever clinical trial of caloric restriction (CR) in humans.

"In keeping with the extraordinary track record of The Journals of Gerontology in multidisciplinary aging studies, the special issue features CR studies ranging from simple unicellular models to human clinical trials," said Biological Sciences Co-Editor-in-Chief Rozalyn M. Anderson, PhD, FGSA, who leads the Metabolism of Aging Research Program at the University of Wisconsin-Madison. "One of the things that people sometimes miss is the amazing fact that aging can be altered; CR research proves this."

The beneficial longevity effect of a simple reduction in calorie intake was first established in rodent studies more than 80 years ago. In the last few decades as genetic techniques have advanced, scientists have made considerable progress in identifying cellular and systemic processes that likely contribute to the increase in disease vulnerability that is associated with aging.

Traditionally, these insights have come from studies of short-lived laboratory animals, but the recent confirmation of the relevance of the CR paradigm to primates has placed renewed emphasis on studies that delve into the mechanisms of delayed aging by CR.

"Remarkably, caloric restriction has been shown to be effective in delaying aging in multiple species and the results in humans look equally promising," Anderson said. "Indeed for many studies, CR is used as the gold-standard for enhanced longevity against which new drugs and anti-aging strategies are measured."

One of the issue's articles reports on the outcomes of the CALERIE study, the first human clinical trial of CR. Conducted across three sites in the U.S., this pioneering work showed not only that CR (without malnutrition) could be tolerated in humans but it also produced beneficial effects on numerous clinical disease risk indices. Using two distinct computation approaches, the authors identified a slower pace of aging in the individuals in the CR group compared to the control subjects. This discovery paves the way for high-resolution molecular studies of the response to CR in humans. These methods may provide a solution for much needed surrogate markers for healthy aging in future clinical trials to identify drugs and diets to enhance healthy aging.

"Ultimately what these studies show is that what you eat influences how you age, and it's not all bad news," Anderson said.