Epigenetics: The Genie in Your Genes

Gerald Larson, PhD, RCEP, CSCSChair/Assistant Professor of Kinesiology

School of Science and HealthAvila University

What is Epigenetics?

• Conrad Waddington (1905-1975) is often credited with coining the term epigenetics in 1942 as “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being”.

• Epigenetics appears in the literature as far back as the mid 19th century, although the conceptual origins date back to Aristotle (384-322 BC).

In biology, and specifically genetics

• In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- (Greek: επί- over, above, outer) -genetics. It refers to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such changes are DNA methylation and histone deacetylation, both of which serve to suppress gene expression without altering the sequence of the silenced genes.

But what do the scientists that work in this rapidly expanding research field have to say?

• “Epigenetics has always been all the weird and wonderful things that can’t be explained by genetics.”Denise Barlow (Vienna, Austria)

• “The difference between genetics and epigenetics can probably be compared to the difference between writing and reading a book. Once a book is written, the text (the genes or DNA: stored information) will be the same in all the copies distributed to the interested audience. However, each individual reader of a given book may interpret the story slightly differently, with varying emotions and projections as they continue to unfold the chapters. In a very similar manner, epigenetics would allow different interpretations of a fixed template (the book or genetic code) and result in different read-outs, dependent upon the variable conditions under which this template is interrogated.”Thomas Jenuwein (Vienna, Austria)

Cell Physiology

Figure 1-39 Molecular Biology of the Cell, Fifth Edition (© Garland Science 2008)

Figure 4-6 Molecular Biology of the Cell (© Garland Science 2008)

Figure 4-35 Molecular Biology of the Cell (© Garland Science 2008)

Cardiovascular Disease

Introduction to Cardiovascular Disease

• Cardiovascular disease leading cause of serious illness and death in United States

• Affects over 80 million Americans

• Accounts for 1/3 of all US deaths annually

• Over $500 billion in annual costs

Figure 21.1

Figure 21.2

Figure 21.3

Forms of Cardiovascular Disease: Coronary Heart Disease

• Atherosclerosis begins early in life– Fatty streaks appear in infancy, childhood– Fatty streaks appear in coronary arteries in teens– Fibrous plaques develop in 20s– Combination of genetics and lifestyle

Obesity and Diabetes

Obesity:Prevalence in the United States

• Prevalence dramatically since ~1980– Prevalence of overweight has not changed much– Obesity continues to increase

• More prevalent in some races and ethnicities– Mexican-American men– Black women

• Increasing prevalence in children and teens

Obesity:Prevalence in the United States

• With age: fat mass , lean body mass – Over age 25, average person gains ~0.7 to 1 lb

per year– Up to 33 extra lb by age 55

• Will have significant effect on health care– Earlier onset of obesity– Increasing rates of obesity– Earlier onset of obesity-related diseases

Figure 22.3

Obesity:Etiology

• Physiological factors– Heredity/genetics– Hormonal imbalances– Altered basic homeostatic mechanisms

• Lifestyle factors– Cultural habits– Inadequate physical activity– Improper diets

Obesity:Health Problems

• Body fat distribution: disease risk factor– Upper-body (android) obesity (men)– Lower-body (gynoid) obesity (women)

• Waist:hip girth ratio and visceral fat index identify fat distribution

• Android obesity higher risk for– Cardiovascular disease– Elevated blood lipids– Diabetes

Figure 22.7

Diabetes:General Treatment

• Type 1 diabetes– Insulin administration– Diet– Exercise

• Type 2 diabetes– Weight loss– Diet– Exercise– Recently developed drugs

Type 2 Diabetes:Role of Physical Activity

• Exercise enhances insulin sensitivity– Muscle contraction mimics insulin action– Lowers blood glucose– Decreases insulin requirement– Short-term (72 h) effect

• Combination of resistance and aerobic training may be optimal

Deep Practice

Wrapping Myelin

Insert Figure 3.2 b