Transcript EPIGENETICS

Epigenetics and
Health Disparities
Part II: Psychosocial Factors
Anita R. Webb, PhD
JPS Health Network
Fort Worth, Texas
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
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.
TOPICS
Stress
Loneliness
Nurturing
Childhood Adversity
Trauma
Obesity
Health Disparities
“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.
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
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.
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
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)
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.
2007;8(9):R189.
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).
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
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)
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
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
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 May10,1986;1(8489)1077-1081
Mechanism? (continued)
Stress, poverty, trauma
May prematurely age DNA
Accelerate telomere shortening
Undermine health lifelong
Shorten life span
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: N>1200)
Buffer: Adult nurturance (attention,
affection, understanding, caring, etc.)
– http://www.sciencedaily.com/releases/
2011/09/110919164503.htm
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.
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.
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.
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, Alzheimer’s
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. 2009;106 (49): 20912-20917.
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) 1–9.
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.doi:10.1371/journal.pone.00108372010
GOAL: Prevention
Reduce/prevent inflammation
– Inflammation damages epigenome
– Aspirin reduces inflammation
– Aspirin decreases risk
for certain cancers
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.
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.
“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)
Recommended Reading
– Azar B. Psychology of Cells. Monitor on
Psychology, May 2011, 42(5):32.
– Cloud J. Why DNA isn’t your destiny. Time
http://www.time.com/time/magazine/article/0,9
171,1952313,00.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.