Calorie Restriction Mimetics – Slowing Aging by Taking a Pill

What if you could get calorie restriction benefits just by taking a pill that mimics effects and produces CR benefits? Often referred to as calorie restriction mimetics, these substances have been the subject of intense investigation – and with good reason: Some who find it hard to limit their calorie intake could improve their health anyway. Others who are already quite slim could get the extraordinary health and longevity benefits of calorie restriction without risking excessive weight loss.

George RothShould calorie restriction mimetics be part of your regimen? George Roth, PhD. – Featured Guest on the Wednesday, May 22, expert teleconference – will help you answer that question. Dr. Roth has a distinguished career as a research scientist who has published more than 375 papers.  He has been Chief of the Molecular Physiology and Genetics Section of the National Institute of Aging, and Acting Chief of the NIA Laboratory of Cellular and Molecular Biology. Currently, he is CEO of Geroscience, which focuses on development of CR mimetics.

Some of his published work predicts longevity, based on biomarkers. His guidance will be invaluable for the forthcoming DNA HACR study.


Relationship between plasma ghrelin, insulin, leptin, interleukin 6, adiponectin, testosterone and longevity in the Baltimore Longitudinal Study of Aging

Aging clinical and experimental research. 2011 Apr;23(2):153-8.

Stenholm S, Metter EJ, Roth GS, Ingram DK, Mattison JA, Taub DD, Ferrucci L.

National Institute on Aging, Clinical Research Branch, Longitudinal Studies Section, Baltimore, MD 21225, USA.




Caloric restriction (CR) is the most robust and reproducible intervention for slowing aging, and maintaining health and vitality in animals. Previous studies found that CR is associated with changes in specific biomarkers in monkeys that were also associated with reduced risk of mortality in healthy men. In this study we examine the association between other potential biomarkers related to CR and extended lifespan in healthy humans.


Based on the Baltimore Longitudinal Study of Aging, “long-lived” participants who survived to at least 90 years of age (n=41, cases) were compared with “short-lived” participants who died between 72-76 years of age (n=31, controls) in the nested case control study. Circulating levels of ghrelin, insulin, leptin, interleukin 6, adiponectin and testosterone were measured from samples collected between the ages 58 to 70 years. Baseline differences between groups were examined with t-test or Wilcoxon test, and mixed effects general linear model was used for a logistic model to differentiate the two groups with multiple measurements on some subjects.


At the time of biomarkers evaluation (58-70 yrs), none of the single biomarker levels was significantly different between the two groups. However, after combining information from multiple biomarkers by adding the z-transformed values, the global score differentiated the long- and short-lived participants (p=0.05).


In their sixties, long-lived and short-lived individuals do not differ in biomarkers that have been associated with CR in animals. However, difference between the groups was only obtained when multiple biomarker dysregulation was considered.

PMID 21743292, NIH, NLM, PubMed access to MEDLINE

DNA HACR will take a lesson from this work: Individual biomarkers cannot be expected to tell the whole story. Instead, as is usual in biosystems, substances and processes affect each other. DNA HACR’s design underlines this: Rather than an experimental cohort, being tested against controls, this study has many studies going on at the same time. We have a great opportunity to learn a great deal.


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