Epigenetics refers to external or environmental factors that can affect how genes are expressed without altering the underlying DNA sequence. A study of individuals who experienced malnutrition prenatally during the Dutch Hunger Winter found they had persistent epigenetic differences decades later, showing how early life experiences can have long-lasting impacts. Additional research demonstrates that parental nutrition, such as a father's betel nut chewing, can influence disease risk in offspring through transgenerational epigenetic effects. Exercise is also shown to induce widespread epigenetic changes related to energy metabolism and inflammation in human muscle tissue. In summary, lifestyle and environmental exposures not only affect personal health but can also impact future generations through epigenetic mechanisms.

1. EPIGENETICS:
YOU ARE WHAT YOU EAT
MICHAEL (KEN) MINDORO, MD

2. DISCLOSURES
• I have no commercial disclosures

3. 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.

5. HERITABILITY

6. GREGOR MENDEL
• Austrian monk (1822-
1884)
• Studied mathematics
and botany; the father
of genetics
• Experimented with pea
plants

9. Y Y
y
y
Yy Yy
Yy Yy

10. Y y
Y
y
YY yY
Yy yy

13. 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.

14. MENDELLIAN INHERITANCE

16. 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

17. HUMAN GENOME PROJECT
• 15-year study to
sequence the entire
human genome.
• Started in 1990,
declared completed in
2003.

18. • “junk DNA”
• Roughly 22,300 protein
coding genes

20. LET’S TALK ABOUT JEANS

28. EPIGENETICS
• Ancient Greek
• επί/epi = 'upon', 'over', 'above‘
• γενετικός/genetikos = 'genitive' > γενεά/genea =
'generation' > γεννώ/geno = 'birth to' >
γένεσις/genesis = 'origin')

29. 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)

33. 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

34. And the LORD God commanded the man, saying, Of
every tree of the garden thou mayest freely eat:
Genesis 2:15-17

35. 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

36. From the very beginning,
mankind understood that
food choices can prolong life
or bring sickness or even death

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

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

39. AUDREY HEPBURN
• Survivor of Dutch Hunger
Winter
• Despite her later wealth,
she had lifelong negative
medical repercussions
• Anemia, respiratory
illnesses, edema

40. • 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

41. • 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.

42. • 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

43. • The babies who were born small stayed small all
their lives, with lower obesity rates than the general
popula­tion.
• 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.

44. • 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?

45. • 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 devel­opment in the
womb that affected them for decades after.

46. • 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.

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

48. • 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.

49. • 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.)

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

51. EXODUS 20:5
• “…visiting the iniquity of the fathers upon the
children unto the third and fourth generation of them
that hate me…”

53. PATERNAL NUTRITION:
INFLUENCES ACROSS
GENERATIONS

54. • 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.

55. • 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

56. METABOLIC SYNDROME
• Increased blood pressure
•
•
•
•

57. METABOLIC SYNDROME
• Increased blood pressure
• High blood sugar
•
•
•

58. METABOLIC SYNDROME
• Increased blood pressure
• High blood sugar
• Excess body fat around
the waist
•
•

59. METABOLIC SYNDROME
• Increased blood pressure
• High blood sugar
• Excess body fat around
the waist
• High triglyceride levels
•

60. METABOLIC SYNDROME
• Increased blood pressure
• High blood sugar
• Excess body fat around
the waist
• High triglyceride levels
• Low HDL

61. • 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.

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

63. • 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…

65. EPIGENETICS:
YOU ARE WHAT YOUR
PARENTS/GRANDPARENTS
EAT
MICHAEL (KEN) MINDORO, MD

66. EZEKIEL 18:19-20
• Yet say ye, Why? doth not the son bear the iniquity
of the father?

67. 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.

68. 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.

69. TWINS

72. • Epigenetic diet: impact on the epigenome and
cancer
• Hardy and Tollefsbol. Epigenomics. 2011 Aug 1;
3(4): 503–518.

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

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

75. • “..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…”

76. INTERMITTENT FASTING

77. • 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.

78. • 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

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

80. • 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

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

84. • 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.

85. • 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

86. • 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.

87. • 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.

88. • Pedaled on a stationary
bicycle 45-minutes,
4x/week for three months
• Exercised leg was more
powerful than the other

89. • 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

90. • 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.

91. • They affect how healthy our muscles become.
• They were not changed in the unexercised leg.

92. EXODUS 20:6
• “And showing mercy unto thousands of them that
love me, and keep my commandments.”

93. • 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.

94. 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

95. • 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.

96. SUMMARY
• Genetics loads the gun; lifestyle pulls the trigger.
• Eat the healthiest plant-based food that you can
afford.
• Stay active
• Moderate stress

97. • 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

98. • 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.

99. 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”

100. QUESTIONS?