Epigenetics and Health Disparities

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Epigenetics and Health Disparities

• Part II Psychosocial Factors
• Anita R. Webb, PhD
• JPS Health Network
• Fort Worth, Texas

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Key Points PART I (Disease)

• Gene expression can be altered by the
  environment, including the social environment.
• Alterations may be passed down to subsequent
  generations.
• Without changes in DNA.
• Epigenetics may explain some diseases.
• Burgeoning field of medicine

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KEY POINTS

• PART II
• Stress can affect how our genes are expressed
  (through multiple generations).
• Epigenetics theory may contribute to the
  understanding of health disparities.
• Epigenetics research is suggesting how therapies
  can reverse genetic damage and diseases such as
  cancer.

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TOPICS

• Stress
• Loneliness
• Nurturing
• Childhood Adversity
• Trauma
• Obesity
• Health Disparities

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Social Genomics

• Our interpersonal world exerts biologically
  significant effects
• On the molecular composition of
  the human body.
• Hollander RS. Social genomics Genomic inventions
  in society. Science Eng. 2002,8(4)485-496.
• Genetic inheritance is not altered.
• Expression is altered.

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Stress and Disease

• Psychosocial stress may affect basic cellular
  functions and metabolism,
• Lifestyle diseases e.g. cardiac, diabetes
• And change gene expression
• Without changing DNA.
• i.e. Epigenetic changes
• Embryos and infants may be especially sensitive

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Stress and Telomeres

• Stress can accelerate telomere shortening
• (protective endcaps on chromosomes).
• Emotional stress releases cortisol.
• Cortisol can damage healthy tissue.
• Cell repair requires additional cell divisions.
• Each cell division shortens telomeres.
• So that telomeres provide less protection.
• Result DNA ages more rapidly.

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Further Stress Damage

• Immune cells patrol the body
• First line of defense against infection
• Scan for damaged tissue
• Mount inflammatory response
• Chronic stress Chronic inflammation Premature
  telomere shortening Risk for
• Some types of cancer
• Cardiovascular disease
• Neuro-degeneration/cognitive defects

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The Psychology of Cells

• Developmental Plasticity
• The environment makes its way into genes and
  controls what your genome becomes.
• . Example Loneliness (social environment)
• Primes the immune system
• Activates inflammatory response
• Can eventually lead to disease
• (Azar 2011 see last slide)

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Loneliness Research

• White blood cells of lonely subjects
• 1. Over-expressed genes that resulted in
  inflammation
• 2. Under-expressed genes involved in antibody
  production (lymphocytes)
• Cole SW, Hawkley LC, Arevalo JM, Sung CY, Rose
  RM, Cacioppo JT. Social regulation of gene
  expression in human leukocytes. Genome Biol.
  20078(9)R189.

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Example Maternal Nurturing

• Maternal nurturing of rat pups promoted
• DNA methylation at gene which encodes hippocampus
  glucocorticoid receptors
• Result Favorably altered emotionality
• Plus rate of brain and body aging
• Continued to affect pups stress-response pathway
  into adulthood.
• Weaver IC et al. Epigenetic programming by
  maternal behavior. Neuroscience 7, 847-54 (2004).

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Childhood Adversity

• Poverty, loneliness, deprivation, neglect
• Affect immune function at genetic level
• Pro-inflammatory genes are more active (ready
  for trouble).
• Creates health hazard even into adulthood
• Regardless of adult SES

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Example Childhood Adversity

• Social adversity in childhood
• Tunes immune system to be vigilant for stress
• Primes immune system to use inflammatory response
  
• Increases disease risk
• Cortisol runs rampant
• Immunosuppressive
• Health consequences
• (Azar)

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Chronic Stress or Trauma

• Since stress is associated with telomere
  shortening in immune system cells,
• Traumatized and chronically stressed children are
  at risk for
• Lifelong faulty immune function
• Childhood adversity may contribute to
• Health disparities as adults

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SES Health Disparities Mechanism?

• Early adversity primes immune system to
• Activate inflammatory response.
• May reprogram immune system
• Beginning in the womb
• Increasing risk for disease

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Example Gestation

• Conditions in the womb can affect fetus
• Continuing well into adulthood.
• Example If a pregnant woman eats poorly
• Her child will be at significantly higher risk
• For cardiovascular disease as an adult.
• Barker DJ, Osmond C. Infant mortality, childhood
  nutrition, and ischaemic heart disease in England
  and Wales. Lancet May10,19861(8489)1077-1081

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Mechanism? (continued)

• Stress, poverty, trauma
• May prematurely age DNA
• Accelerate telomere shortening
• Undermine health lifelong
• Shorten life span

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Adult Nurturance

• Much research shows that the stresses that
  disadvantaged children undergo
• Affect their physiological development,
• Making them permanently vulnerable to infection
  and disease. (MIDUS Ngt1200)
• Buffer Adult nurturance (attention, affection,
  understanding, caring, etc.)
• http//www.sciencedaily.com/releases/
  2011/09/110919164503.htm

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Other Implications OBESITY

• During times of food scarcity
• Physiology becomes more efficient in storing
  calories to protect against starvation.
• Efficient food storage mechanisms will be passed
  to subsequent generations.
• If food later becomes more plentiful
• Descendants will be at higher risk for obesity
• Due to more efficient food storage.

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Epigenetic Changes

• Can be inherited by multiple generations
• Via epigenetic marks
• But is NOT evolution
• Does NOT change DNA
• When the environmental stressor is removed, the
  epigenetic mark fades
• DNA eventually reverts to original programming in
  a subsequent generation.

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Epigenetic Therapy

• Unlike genome, epigenome can be modified
• Therefore Can be CORRECTED
• Therapy Change cells instructions
• 1. Tell genes which play a role in disease to
  Lie dormant.
• 2. Reactivate original cell instructions that
  were silenced by disease.

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VIA Epigenetic Marks

• Learn how to manipulate epigenetic marks
• Develop drugs that can
• Silence bad genes
• Activate good genes
• FDA approved epigenetic drug to treat rare deadly
  blood malignancies (MDS) (2004)
• Future targets Cancers, schizophrenia, autism,
  diabetes, Alzheimers

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Example Stress and the Brain

• Acute stress caused rapid chemical change in rat
  brains.
• Hippocampus Memory
• Especially susceptible to stress
• Fluoxetine (Prozac) reversed some methylation
  effects of chronic stress.
• Hunter RG, et al. Regulation of hippocampal H3
  histone methylation by acute and chronic stress.
  Natn Acad Sc. 2009106 (49) 20912-20917.

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Treatment Research Repairing Telomere Damage

• Women with cervical cancer
• Treatment Stress management training
• Six sessions of telephone counseling
• Reduced emotional stress
• Promoted telomere repair and growth
• Drury, Theall, Gleason et al. Telomere length and
  early severe social deprivation linking early
  adversity and cellular aging. Molecular
  Psychiatry, (2011) 19.

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Prevention Research

• Women Post-menopausal, dementia caregivers
• Vigorous physical exercise
• Increased heart rate and/or sweating.
• At least 14 minutes a day
• Was related to longer telomeres,
• Puterman E. et al. Power of Exercise Buffering
  the Effect of Chronic Stress on Telomere Length.
  PLoS One, May 2010, 5(5)e10837.
  e10837.doi10.1371/journal.pone.00108372010

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• GOAL Prevention
• Reduce/prevent inflammation
• Inflammation damages epigenome
• Aspirin reduces inflammation
• Aspirin decreases risk
  for certain cancers

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SUMMARY of Part II

• Epigenetics explores how the environment can
  change gene expression.
• Inflammation damages the epigenome.
• The most important developmental era for the
  epigenome is during fetal development.
• Stress and social adversity trigger inflammatory
  response, disease.
• Contributes to health disparities.
• Rapidly growing research field.

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Key Points

• Gene expression can be altered by the
  environment.
• The alteration can be passed down to subsequent
  generations.
• Contributes to health disparities.
• Suggests new therapies to reverse genetic damage
  and disease.

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The social environment molds and shapes the
expression of our genetic heritage until the
genetic contribution is sometimes barely
evident. Social relationships clearly
forge our underlying biology. Shelley E.
Taylor, PhD. The tending instinct How
nurturing is essential to who we are and how
we live. (2002)
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Recommended Reading

• Azar B. Psychology of Cells. Monitor on
  Psychology, May 2011, 42(5)32.
• Cloud J. Why DNA isnt your destiny. Time
  http//www.time.com/time/magazine/article/0,9171,1
  952313,00.html. (Jan.6,2011).
• Hampton T. Studies probe role of telomere length.
  JAMA 2011,305(22)2278-2279.
• Stein R.A. Epigenetics the link between
  infectious diseases and cancer. JAMA 2011,
  305(4)1484-5.