Research being conducted in the laboratory of Roman V. Kondratov, PhD, from COSHP's Center for Gene Regulation in Health and Disease (GRHD) is helping unravel the mystery of aging. The National Institute of Aging recently renewed Dr. Kondratov's R01 grant titled, "Circadian clock and dietary restriction." Data obtained as a result of this study will help to understand the molecular basis of aging and to develop physiological and pharmacological strategies for the treatment and prevention of age-associated pathologies. 

Over the last decade, research has found that dietary restriction (i.e., reducing calorie intake without malnutrition) is a powerful intervention for increasing longevity in a variety of organisms. Specifically, calorie restriction may reduce the occurrence of age-associated diseases, including osteoporosis, diabetes, heart disease, neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as cancer. In contrast, disruption of the body's circadian rhythms has been associated with the negative effects of aging on physiology, metabolism, and behavior. 

Dr. Kondatov and his associates have uncovered biochemical clues to how these opposing mechanisms may function. The team is studying the master circadian clock, located in the hypothalamus region of the brain. It consists of a cluster of specialized nerve cells called the suprachiasmatic nucleus (SCN). The SCN generates rhythmic electrical pulses in response to changes in the wake-sleep cycle, which signal peripheral clocks in tissues such as the liver, heart, and muscles [1]. Rhythmic effects of the sleep-wake cycle cause changes in gene and protein expression, as well as protein and hormone secretion. This in turn controls and coordinates the function of diverse organs and synchronize bodily activities with the environment. 

Dr. Kondratov and his students also observed that the circadian clock may play a key role in maintenance of a healthy skeletal system. CSU doctoral student William Samsa, now a fellow at Case Western Reserve University, demonstrated that mice bred to be deficient in circadian rhythms have lower bone mass and accelerated bone aging compared with normal mice [2]. This highly-regarded research was honored by a Research Highlights editorial in the prestigious journal, Nature Reviews in Rheumatology [3]. 

Another area of research in Dr. Kondratov's lab is an exploration of how disrupting the circadian clock impacts health and longevity. Shift work, poor quality sleep, and jet lag disrupt the circadian clock. These activities prompt us to consume excess calories and, in some cases, increase the risk of disease. The team's pioneering research into the effect of calorie restriction found that disruption of the circadian system leads to accelerated aging and dramatically reduced lifespan in mice. More importantly, calorie restriction does not work if the circadian clock is not functional or in tune with the environment. Further research is required to determine if calorie restriction and/or manipulation of the biological clock can delay aging or extend quality of life.

Dr. Kondratov was recently appointed to the National Institutes for Health (NIH)'s Cellular Signaling and Regulatory Systems Study Section, Center for Scientific Review for the term beginning July 1, 2017. Members are selected on the basis of achievement in their scientific discipline. Over the past 8 years, Dr. Kondratov has brought more than $3M in NIH funding to CSU.

REFERENCES

1. Kondratova AA and Kondratov RV. Nat Rev Neurosci. 2012 Mar 7;13(5):325-35. doi: 10.1038/nrn3208. 
2. Samsa WE, et al. Bone. 2016 Mar;84:194-203. doi: 10.1016/j.bone.2016.01.006. Epub 2016 Jan 14.
3. Lieben L. Nat Rev Rheumatol. 2016 Mar;12(3):132. doi: 10.1038/nrrheum.2016.10. Epub 2016 Feb 4.