EPIGENETICS: YOU ARE WHAT YOU EATMICHAEL (KEN) MINDORO, MD

DISCLOSURES

• I have no commercial disclosures

A BRIEF SURVEY

• Please raise your hand if this is true for you:

• I have heard of epigenetics before this lecture.• I am moderately conversant on the topic of

epigenetics.• I am moderately conversant on the topic of

healthy living.

HERITABILITY

GREGOR MENDEL

• Austrian monk (1822-1884)• Studied mathematics

and botany; the father of genetics• Experimented with

pea plants

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Yy YyYy Yy

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GREGOR MENDEL

• Mendel’s success was partially due to his choice of pea plants.

• Each gene came in just two different versions, or alleles, which had a clear-cut dominance relationship.

MENDELLIAN INHERITANCE

DNA FUN FACTS

• There are six feet of DNA in nearly every cell of your body.• Your body contains approximately 37 trillion

cells.• If all the DNA in your body were laid end-on-

end, it would reach 30 times the distance from the Earth to the Sun

HUMAN GENOME PROJECT

• 15-year study to sequence the entire human genome.• Started in 1990,

declared completed in 2003.

• “junk DNA”

• Roughly 22,300 protein coding genes

LET’S TALK ABOUT JEANS

EPIGENETICS

• Ancient Greek • επί/epi = 'upon', 'over', 'above‘• γενετικός/genetikos = 'genitive' >

γενεά/genea = 'generation' > γεννώ/geno = 'birth to' > γένεσις/genesis = 'origin')

EPIGENETICS

• The study of how external/environmental factors affects how genes are turned on and off within a given species

• Heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression

• (bookmarks in a cookbook)

And the LORD God took the man, and put him into the garden of Eden to dress it and to keep it.

Genesis 2:15-17

And the LORD God commanded the man, saying, Of every tree of the garden thou mayest freely eat:

Genesis 2:15-17

And the LORD God commanded the man, saying, Of every tree of the garden thou mayest freely eat:But of the tree of the knowledge of good and evil, thou shalt not eat of it: for in the day that thou eatest thereof thou shalt surely die.

Genesis 2:15-17

From the very beginning, mankind understood that

food choices can prolong lifeor bring sickness or even death

DUTCH HUNGER WINTER

• German blockade caused a famine in German-occupied Netherlands in 1944-1945• 4.5 million affected• 22,000 died• Industrialized country

THE DUTCH SUR VIVORS WERE A WELL-DEFINED GROUP OF INDIVIDUALS ALL OF WHOM SUFFERED JUST ONE PERIOD OF MALNUTRITION, ALL OF THEM AT EXACTLY THE SAME TIME.

AUDREY HEPBURN

• Survivor of Dutch Hunger Winter

• Despite her later wealth, she had lifelong negative medical repercussions• Anemia, respiratory

illnesses, edema

• Children of the women who were pregnant during the famine were smaller, as expected. • When these children

grew up and had children those children were also be smaller than average

• If a mother was well fed around the time of conception and malnourished only for the last few months of the pregnancy, her baby was likely to be born small.

• If, on the other hand, the mother suffered malnutrition only for the first three months of the pregnancy but then was well fed, she was likely to have a normal-size baby

• The babies who were born small stayed small all their lives, with lower obesity rates than the general popula tion. • For forty or more years, those people had

access to as much food as they wanted, and yet their bodies never got over the early period of malnutrition.

• Why not? How did their early life experiences affect these individuals for decades? Why weren’t they able to go back to normal once their environment reverted to the way it should be?

• Children whose mothers had been malnourished only early in pregnancy had higher obesity rates than normal. • Greater incidence of other health problems as well,

including effects on certain measures of mental health. • Even though those individuals had seemed perfectly

healthy at birth, something had happened to their devel opment in the womb that affected them for decades after.

• And it wasn’t just the fact that something had happened that mattered, it was when it happened.• Events that take place in the first three

months of gestation, a stage when the fetus is really very small and developing very rapidly, can affect an individual for the rest of his or her life.

• Some of these effects seem to be present in the children of this group, that is, in the grandchildren of the women who were malnour ished during the first three months of their pregnancy. • So something that happened in one pregnant

population affected their children’s children.

• Persistent epigenetic differences associated with prenatal exposure to famine in humans• Heijmans et al. Proc Natl Acad Sci U S A.

2008 Nov 4; 105(44): 17046–17049.

• Individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944–45 had, 6 decades later, less DNA methylation of the imprinted IGF2 (Insulin-like growth factor 2) gene compared with their unexposed, same-sex siblings

• (IGF2 plays an essential role in growth and development before birth.)

• Early-life (intra-uterine) environmental conditions can cause epigenetic changes in humans that persist throughout life

EXODUS 20:5

• “…visiting the iniquity of the fathers upon the children unto the third and fourth generation of them that hate me…”

PATERNAL NUTRITION: INFLUENCES ACROSS GENERATIONS

• Lin et al. Betel nut chewing is associated with increased risk of cardiovascular disease and all-cause mortality in Taiwanese men. Am J Clin Nutr. 2008;87:1204–11

• Chewing betel nut increases the risk of developing metabolic syndrome.

• Chen et al. Transgenerational effects of betel-quid chewing on the development of the metabolic syndrome in the Keelung Community-based Integrated Screening. Program Am J Clin Nutr. 2006;83:688–92.• duration and quantity of betel nut intake by

males is positively related to the risk of their own offspring developing metabolic syndrome

METABOLIC SYNDROME

• Increased blood pressure• •

• •

METABOLIC SYNDROME

• Increased blood pressure• High blood sugar•

• •

METABOLIC SYNDROME

• Increased blood pressure• High blood sugar• Excess body fat

around the waist• •

METABOLIC SYNDROME

• Increased blood pressure• High blood sugar• Excess body fat

around the waist• High triglyceride levels•

METABOLIC SYNDROME

• Increased blood pressure• High blood sugar• Excess body fat

around the waist• High triglyceride levels• Low HDL

• Del Curto et al. Nutrition and reproduction: links to epigenetics and metabolic syndrome in offspring. Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):385-91.

• Maternal nutritional imbalance, either through global nutritional manipulation or deficiencies in select nutrients, predisposes the offspring to metabolic disease.

• Paternal nutritional imbalance also increases the likelihood of metabolic disease in offspring through similar epigenetic mechanisms.

• Paternal nutritional imbalance also increases the likelihood of metabolic disease in offspring through similar epigenetic mechanisms.• …dietary intervention with select nutrients

has been shown to ameliorate postnatal disease phenotypes in offspring…

EPIGENETICS: YOU ARE WHAT YOUR PARENTS/GRANDPARENTS EATMICHAEL (KEN) MINDORO, MD

EZEKIEL 18:19-20

• Yet say ye, Why? doth not the son bear the iniquity of the father?

EZEKIEL 18:19-20

• Yet say ye, Why? doth not the son bear the iniquity of the father? When the son hath done that which is lawful and right, and hath kept all my statutes, and hath done them, he shall surely live.

EZEKIEL 18:19-20

• The soul that sinneth, it shall die. The son shall not bear the iniquity of the father, neither shall the father bear the iniquity of the son: the righteousness of the righteous shall be upon him, and the wickedness of the wicked shall be upon him.

TWINS

• Epigenetic diet: impact on the epigenome and cancer• Hardy and Tollefsbol. Epigenomics. 2011 Aug

1; 3(4): 503–518.

• “A number of bioactive dietary factors …display anticancer properties and may play a role in cancer prevention.”

• “…consumption of dietary agents can alter normal epigenetic states as well as reverse abnormal gene activation or silencing.”

• “..nutritional factors, drugs, chemicals used in pesticides, environmental compounds and inorganic contaminants (i.e., arsenic) can alter the epigenome, and may contribute to the development of abnormalities. It has become increasingly clear that environmentally induced epigenetic changes can be mediated, in part, by diet…”

INTERMITTENT FASTING

• Practicality of Intermittent Fasting in Humans and its Effect on Oxidative Stress and Genes Related to Aging and Metabolism

• Wegman et al. Rejuvenation Research. April 2015, 18(2): 162-172. doi:10.1089/rej.2014.1624.

• 24 participants• Alternated one day of eating 175% of their

usual daily intake with one day of eating 25% of their caloric intake for three weeks

• An average male (70 kg)• 4550 calories on feasting days• 650 calories on fasting days

• Over the next 10 weeks, researchers found that intermittent fasting caused a slight increase to SIRT3, a well-known gene that promotes longevity and is involved in protective cell responses

• If the body is intermittently exposed to low levels of oxidative stress, it can build a better response to it

• An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training.• Lindholm et al. Epigenetics. 2014

Dec;9(12):1557-69.

• Karolinska Institute (Stockholm)• 23 young and healthy men and women• Physical performance and medical tests,

including muscle biopsy• Exercise half of their lower bodies for three

months

• One of the obstacles in the past to precisely studying epigenetic changes has been that so many aspects of our lives affect our methylation patterns, making it difficult to isolate the effects of exercise from those of diet or other behaviors.

• By exercising just one leg, each volunteer became his or her own control group.

• The scientists hypothesized that the exercising leg would show changes related to exercise.

• Pedaled on a stationary bicycle 45-minutes, 4x/week for three months

• Exercised leg was more powerful than the other

• More than 5,000 sites on the genome of muscle cells from the exercised leg now featured new methylation patterns• Some showed more methyl groups; some

fewer

• Many of the changes were on portions known as enhancers that can amplify the expression of proteins by genes

• Most of the genes in question play a role in energy metabolism, insulin response, and inflammation within muscles.

• They affect how healthy our muscles become.

• They were not changed in the unexercised leg.

EXODUS 20:6

• “And showing mercy unto thousands of them that love me, and keep my commandments.”

• Although you may experience long-term effects caused by negative choices made by your ancestors…

• …you may also experience the direct benefits of making healthy choices today.

SWITCHING OFF CANCER?

• Mouse study• Myc oncogene (engineered to be turned off by

doxycycline)• Withholding doxycycline caused liver cancer

cells to develop• Feeding doxycycline eliminated aggressive,

incurable liver tumors in mice in just four weeks

• Green-tagged liver cells• Again feeding the mice doxycycline turned

off the modified Myc gene and eliminated the cancer.• Green cells remained, showing that turning

off the Myc gene alters the cell’s fate rather than killing it outright.

SUMMARY

• Genetics loads the gun; lifestyle pulls the trigger.• Eat the healthiest plant-based food that you

can afford.• Stay active• Moderate stress

• The health of a house depends on:

1. The soundness of its plan of construction

2. The quality of the materials used

3. The care with which it is built

• So too, does your own health depend upon learning God’s health plan, choosing the food He has selected, and caring for yourself as He has indicated.

1 CORINTHIANS 6:19-20

• “…know ye not that your body is the temple of the Holy Ghost which is in you, which ye have of God, and ye are not your own? For ye are bought with a price: therefore glorify God in your body, and in your spirit, which are God’s”

QUESTIONS?