Epigenetics and Health. How well do you fit into your genes?

1. Epigenetics and Health. How well do you fit into your genes? Mark Pettus MD February 18, 2014

2. The proposition • All health and disease are byproducts of complex individualized gene-environment interactions that may go back more than a generation before conception and continue throughout our lives. • Your DNA i.e., your “Book of Life” have a Stone Age imperative, not often compatible with 21st century environmental inputs. • This incompatibility creates a distorted metabolic trajectory that forms the basis of chronic complex disease. • Through epigenomic alteration, our gene expression patterns can be profoundly modulated to promote optimal function and health. • This remains possible throughout life by aligning one’s environmental inputs with that which one’s genes are best suited for.

4. “It’s not what we don’t know that gets us into trouble. It’s what we know that ain’t so.” Will Rogers So what do we know that ain’t so? DNA is indeed plastic!

6. The Epigenome How our “Book of Life” is interpreted and ultimately written.

12. Randy Jirtle MD Duke University “Genomic Stability”

18. Michael Skinner and Transgenerational Epigenomics • “The ability of environmental factors to promote a disease state not only for the individual but also subsequent progeny for successive generations is termed transgenerational inheritance.” • “Epigenetic changes in methylation of the genome of germ cells after specific environmental toxin exposure that become permanently programmed allow transmission of epigenetic transgenerational phenotypes. M Skinner Trends Endocrinol Metab 2010: 21: 214-22

19. Representative Clinical Conditions Suggested to Have Epigenetic Origins • Type 2 DM and Metabolic Syndrome • Coronary artery disease • Autoimmune Diseases • Cancer • Allergic Disorders • Depression • Neurologic: Alzheimer’s, PD, ALS, Autism

20. Lifestyle-Behavioral Factors Shown to Have Health-Promoting Epigenomic Influences • Plant-based, unprocessed foods • Movement • Mindfulness • Bonding-social connection • Reduction in Environmental Toxin exposure • Microbiome

23. Different carbohydrates produce unique genomic responses! High Glycemic Carbs Low Glycemic Carbs 62 genes regulating Same genes turned off; Inflammation, stress, Genes regulating same insulin sensitivity production turned off. Immune responses Kalle et al. Am J Clin Nutr;2007:851:1417-27

27. Xenohormesis

28. DIABETES CARE, VOLUME 34, APRIL 2011 Diabetes Care 34:1014–1018, 2011 CONCLUSIONS Exposure to the Chinese famine during fetal life or infancy is associated with an increased risk of metabolic syndrome in adulthood. These associations are stronger among subjects with a Western dietary pattern. Famine studies may give direct evidence for the hypotheses that early malnutrition plays a role in the origins of hypertension, insulin resistance, central obesity, and dyslipidemia, which are all components of the metabolic syndrome. Fetal famine exposure has been shown to be associated with the risk of hypertension in later life in subjects exposed to the Dutch Hunger Winter (1944–1945), Leningrad Siege (1941–1944), and Chinese famine (1959–1961). Prenatal exposure to both the Dutch Hunger Winter and Chinese famine was also associated with impaired glucose tolerance among adults. Maternal famine exposure during gestation was also associated with higher BMI and waist circumference in Dutch and Chinese women and a more atherogenic lipid profile among Dutch adults.

29. After as little as 30 minutes of interval intensity exercise, methylation patterns change significantly in skeletal muscle.

30. Changes in methylation patterns impacting several metabolic pathways e.g. lipogenesis are seen before and after 6 month exercise program in human adipose cells.

33. MBSR and Reduction in Inflammatory Biomarkers

39. Thank you.