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Research In Action 2021

Photo Research in Action Patrick Grant

Can You Turn Your Genes On and Off?

Patrick Grant, Ph.D.
Associate Professor, Biomedical Science,
Charles E. Schmidt College of Medicine

Can fasting cause autophagy and does autophagy account for reversing aging as well?    

Yes, the literature suggests fasting and caloric restriction stimulate autophagy.

Can you just review some of the important findings in the exercise and addiction study?    

In collaboration with the lab of Dr. Wendy Lynch at the University of Virginia, we found that exercise initiated during early, but not late abstinence from cocaine, reduced cocaine-seeking behavior. This effect was strongly associated with dorsal medial prefrontal cortex (dmPFC) Grm5 expression (gene encoding metabotropic glutamate receptor 5), and modestly associated with Grin1 and Bdnf-IV expression. Activation of Glu5 in the dmPFC during early abstinence mimicked the efficacy of early-initiated exercise. However, our results suggest there may be redundancy in the mechanisms through which exercise reduces cocaine-seeking. We are now tracking all gene changes in this model.

Have you had any connection with the genetic Holocaust DNA studies?    

I do not have any connection with these studies.

For transgenerational effects to take place you must assume that cells in the germile care the epigenetics changes. But there is also evidence that this is not always true. Do you have evidence from your lab about that?    

No, we have not studied this.

I heard the effects of caloric restriction is so restrictive that it cannot be studied ethically in humans.    

I am aware of two pilot clinical trials in healthy humans. One involved a periodic diet that mimics fasting (five days of caloric restriction per month for three months). The other followed volunteers who reduced their caloric intake by 15% over two years. These have shown that dietary restriction decreases the levels of systemic biomarkers of ageing and lowers the levels of multiple risk factors for cancer and cardiovascular diseases, supporting the notion that dietary restriction increases health span in humans. See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886711/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509734/

How do you distinguish between effects as a result of genetic and epigenetic?    

Genetic effects involve an alteration of DNA sequence. Epigenetic changes do not alter DNA sequence and are reversible.

Expound on type of diet men ate in the late 1800s for the study in Sweden.    

My understanding is that the Överkalix study tracked regional harvest statistics, grain prices and other local records as an indicator of food intake. They kept livestock (pigs and cattle), ate salmon, but a good harvest provided enough barley and rye to get them and their animals through a six-month winter. In years of poor harvest/crop failure, residents of Överkalix hunted small birds and ate bark-bread (made from the inner bark of fir trees).

Link for questions answered?    

This article reviews many of the research studies of epigenetics and aging: https://www.nature.com/articles/s41580-019-0204-5.