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Circadian Rhythms a Key to Aging


One of the key interdisciplinary themes of our IGERT is on understanding the basic mechanisms of aging, with emphases on examining processes of change in multiple domains (cellular to societal). Professor Giebultowicz and IGERT trainee Kuntol Rakshit are conducting ground-breaking work on understanding how circadian rhythms may affect basic aging processes at the genetic level. They use fruitflies to investigate how biological clocks change with age. One of the symptoms of aging in humans is that their sleep is not as sound as in young individuals and similar remarkable changes are observed in aging fruitflies. Their prior work determined that biological clocks in old organisms become weak due to reduced expression of certain clock genes. The challenging question that they are addressing in ongoing experiments is whether aging clock mechanism can be repaired by genetic manipulations, leading to improved sleep activity rhythms, and better brain health. Participation in the IGERT program inspired their research team to initiate research in two new directions. First, they learned that researchers in the Musculoskeletal Core investigate ways to preserve mobility, balance, and strength through the lifespan in humans. This prompted them to test whether exercise improves mobility in aging flies. Indeed, they found that age-related disruption of biological clocks weakens motor performance. Another new direction in their research was stimulated by investigations in the Psychosocial Core on the effects of stress on aging and lifespan in humans. They devised a test to challenge flies with a non-lethal stressor and observed that this negatively affects lifespan in flies with disrupted circadian clocks. These studies were directly linked to the interdisciplinary nature of our IGERT that provided a broader perspective inspiring new directions for their research. This research is important because biological clocks coordinate many cellular and physiological functions, and their disruption is connected to metabolic and neurological diseases in humans. Because clocks have similar genetic mechanism in flies and humans, their research may help to understand how strong clocks may prevent age-related diseases.

Recently published work can be found in:

Krishnan, N., Rakshit, K.*, Chow, E., Wentzell, J.S., Kretzschmar, D. & Giebultowicz, J.M. (2012) Loss of circadian clock accelerates aging in neurodegeneration-prone mutants. Neurobiology of Disease, 45 (3): 1129-1135. doi:10.1016/j.nbd.2011.12.034

Rakshit, K.*, Krishnan, N., Guzik, E.M., Pyza, E. & Giebultowicz, J.M. (2012) Aging dampens the molecular circadian oscillations in Drosophila. Chronobiology International, 29 (1): 1-10. (IF-5.5).

Address Goals

This research on circadian rhythms is an innovative approach to understanding some of the biological/physical effects of aging that, potentially, could have consequences for humans. Although translational research with humans needs to be conducted, what we are learning in a model organism (fruitflies) could offer insights into improved quality of life for aging humans. For instance, if we could discover how to optimize circadian rhythms we might potentially improve sleep patterns and lessen cognitive declines associated with normal aging, as well as more severe declines associated with neurodegenerative diseases such as Alzheimer’s disease.