Longevity Research Program:
Director: John O. Holloszy, M.D.
Co-Director: Luigi Fontana, M.D., Ph.D.
Project Overview:
The Longevity Research Program studies of caloric restriction (CR) have provided, and continue to provide, important new information regarding human aging and the ability to extend the healthy, disease-free component of human lifespans (see grants funded by LLF in 2008 and 2009).
While severe CR has been shown to have major health and anti-aging benefits in humans, it also has unpleasant side effects, such as emaciation, amenorrhea in premenopausal women, decreased sex drive and feelings of chronic hunger. That might prevent most health-conscious individuals from practicing CR over the long term. There is also the question of whether CR has the same life-extending and anti-cancer effects for humans as it does for laboratory rodents.
In rodents, CR results in large reductions in levels of Insulin-like Growth Factor 1 (IGF-1). Reduction of IGF-1 is known to play a key role in mediating both the life-extending and anti-cancer effects of CR in laboratory animals. However, CR does not by itself result in a decrease in IGF-1 in humans.
In a preliminary three-week experiment involving six CR participants, protein intake was reduced by about one-third, which resulted in a decrease in plasma IGF-1. Based upon this experiment and other available information, protein restriction (PR) might prove to be as, or more, effective than CR in slowing aging and protecting against cancer. PR has the advantage that it is much less difficult to practice than CR, and does not have CR’s unpleasant side effects, so it has much greater applicability and practical relevance than CR.
This year we propose two studies: one where we will investigate the effect of protein restriction on prostate cancer, and one where we will determine if protein restriction slows aging and/or extends maximal lifespan and protects against cancer in laboratory rats.
Progress Report:
Rat Study: In our preliminary study, we found that middle-aged rats cannot tolerate a diet in which only 6% of calories are from protein. However, they are weight stable and appear healthy on a diet in which 7% of calories are from protein. The rats in the longevity study and the subgroup that will be studied at age 28 months have now been on the low protein diet (7%) for five (5) months.
Studies on patients with prostate cancer: Regarding the study on prostate cancer patients, obtaining regulatory approval from the Siteman Cancer Center and then from the IRB took 7.5 months. We have enrolled nine (9) participants, and an additional 10 are waiting to go through screening.
