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Nutrition Beyond Calories &
the Role Trees can play
Navin Sharma
Science Seminar – 25 April 2014

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• How knowledge is changing and how this will lead to future nutrition
• Double burden of nutrition
• Maternal nutrition and evolution of epigenetics
• From single molecule to total calories – a case study of aging research
• What will be the roles of trees?
DNA controling you  environment controlling you 
maternal nutrition  Mind controlling you??
Theme of the Seminar

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Exogenous plant MIR168a specifically targets mammalian LDLRAP1:
evidence of cross-kingdom regulation by microRNA. Zhang L et al. Cell
Res. 2012 Jan;22(1):107-26
• Discovered plant micoRNAs in the serum of mice and humans.
• The microRNAs possibly came from ingested rice.
• The microRNA MI168a binds to the mRNA of low-density lipoprotein
receptor adapter protein 1, inhibiting its translation.
• Decrease LDL removal from plasma
• Ingested plant microRNAs can regulate the expression of human genes.
Micro RNA from food can be found in blood stream
MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs
and triggering either translation repression or RNA degradation

4. 4
Royal jelly is a complex, protein-rich substance secreted from
glands on the heads of worker bees.
To be queen larva is fed royal jelly inside a compartment
called a queen cup.
The workers and queens are genetically identical.
The royal jelly diet makes the queen: develops ovaries and a
larger abdomen for egg laying,
The worker are sterile.
The royal jelly silences a key gene (Dnmt3), which codes for
an enzyme that silences a group of queen genes. When
Dnmt3 is turned "on," the queen genes are epigenetically
silenced, and the larvae develop into the default "worker"
variety.
To be Queen – need special diet
Science. 2008 Mar 28;319(5871):1827-30.
"Genetic Science Learning Center, University of Utah, http://learn.genetics.utah.edu."

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Jerdon’s Jumping Ant
Florida Carpenter Ant
ANT GENOME SEQUENCING –
WAY TO UNDERSTAND LONGEVITY
• In 2010 – The Ant Genome sequenced
• Jerdon‟s Jumping Ant & Florida Carpenter Ant
• Very Different Social Structure
• In Jumping Ant – Queen replaceable
• New Queen Fed Special Diet – Lives 10- times Longer
Up-regulation of telomerase and sirtuin deacetylases in longer-lived H. saltator
reproductives, caste-specific expression of microRNAs and SMYD histone
methyltransferases, and differential regulation of genes implicated in neuronal
function and chemical communication
Science (2010) – 329: 1068-1071

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Malnutrition, per capita calories, Prevalence of diabetes and
CVD
Malnutrition Calories
Diabetes CVD

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Source: Global Health Risks (2009)
Nutritional Double Burden

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• Famine exposure in first 2 trimesters lead to 80% higher prevalence of overweight
(p<0.0005)
• Famine exposure in last trimester or famine exposure in first 5 months of life
associated with 40% lower prevalence of overweight (p<0.005)
Obesity in Young Men after Famine Exposure in Utero and
early Infancy (Ravelli et al NEJM, 1976)

9. The Fetal Origins or “Barker” Hypothesis
• Pioneered by David Barker in the early 1990s
– Painstaking development of historical birth cohort studies in
England
– Poor nutrition of mother during pregnancy: 2-fold increase
in coronary heart disease from largest to smallest BW &
Impaired GT increased from 14% to 40%
• Impaired fetal growth causes adult disease
• “Thrifty phenotype” - impaired fetal growth permanently
changes the body‟s structure and physiology
– Adaptive for compromised nutrition
– Maladaptive for over-nutrition
• Potential mechanisms include blood pressure & glucose
tolerance
Am J Clin Nutr 2000 71: 1344S-1352S.

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Yellow Mouse Agouti Mouse
Maternal Supplements
with
zinc
methionine
choline
folate
B12
•High risk
cancer, diabetes, obesity
•Reduced lifespan
•Lower risk of
cancer, diabetes, obesity
• Prolonged life
LTR Hypomethylated LTR Hypermethylated
Hypermethylation leads to increase in lifespan and decrease in metabolic disorders
Cooneyetal.(2002)JNutr.132:2393S
Mother’s nutrition and epigenetic changes
"Genetic Science Learning Center, University of Utah, http://learn.genetics.utah.edu."

12. NUTRITION & HEALTH IN „OMICS ERA: EPIGENETICS
• CpG- Cytosine Phosphate
• Can be methylated to generate 5-methyl
cytosine
• Spontaneously deaminates to form
Thymine
• Poorly recognized by DNA repair
mechanism
• Thus CG  TG mutation propagates
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Changes in gene expression, cellular memory, reversible, no change in DNA structure

13. Homeostasis Broken Down with methylation
Disease : Outcome of interaction of DNA and Food components

14. Figure 4. Resveratrol induces overall hyperacetylation in HepG2 but not Hep3B or HuH7 cells.
Venturelli S, Berger A, Böcker A, Busch C, et al. (2013) Resveratrol as a Pan-HDAC Inhibitor Alters the Acetylation
Status of Jistone Proteins in Human-Derived Hepatoblastoma Cells. PLoS ONE 8(8): e73097.
doi:10.1371/journal.pone.0073097
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073097

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Nutrient or diet Epigenetic mechanism
Embryonic development Folate DNA methylation, imprinting
Choline DNA methylation
Protein restriction
DNA methylation, histone
modifications
Alcohol DNA methylation
Stem cell Butyrate
Histone acetylation, DNA
methylation
Retinoic acid PRC
Aging Folate DNA methylation
Calorie restriction Histone acetylation
Immune function Folate DNA methylation
Cancer Methyl-deficient diet Histone modification, microRNA
Genistein DNA methylation, microRNA
(−)-Epigallocatechin-3-gallate DNA methylation, PRC
Curcumin microRNA
Obesity, insulin resistance High-fat diet DNA methylation, microRNA
Methyl-deficient diet DNA methylation
Curcumin Histone acetylation
Inflammation Resveratrol Histone acetylation
AdoMet Histone methylation
Methyl-deficient diet microRNA
Neurocognition Choline
DNA methylation, histone
methylation

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Add life to age – clear evidence from foods and nutrition
HEALTHY AGEING
http://www.healthandage.com/html/min/eama/eama6/idx/docs/june_2006/TSAL_J_POWELL_Healthy_Ageing.pdf
Oxidative stress appears to be a major
determinant of life-span accessible to
nutritional intervention.

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SMR-Specificmetabolicrate
Increase in SOD may act as a determinant in longevity
ANTIOXIDANTS AND AGEING
AmJC/inNutr1991;53:373S-9S
MLSP- Maximum lifespan potential

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ANTIOXIDANTS AND LIFESPAN
Increased concentration of antioxidants help in longevity
AmJClinNutr1991;53:373S-9S

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Sod 2 null mutants show decreased life span in Drosophila
Genetics165:2295–2299(December2003)
A Sod2 NULL MUTATION IN DROSOPHILA

20. Life-span and superoxide dismutase/catalase
mimetics
Small synthetic mimetics increases the
mean life-span of C elegans by 44 %,
and treatment of prematurely aging
worms resulted in normalization of their
life-span (a 67 % increase).
MelovSScience2000Sep1;289(5484):1567-9

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SOD 1 expression is higher in Male ant when compared to Queen
SOD1 gene expression as measured
by Northern blots
Sod1 EXPRESSION IN ANTS
SOD1 activity assay levels in
activity units per milligram
Lasius niger (Ant)
Queens reach an
age of 28 years,
whereas workers
for 1-2 years and
males, a few weeks
3486–3489 PNAS March 9, 2004 vol. 101 no. 10
Oops!!

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sod-2 mutant worms live significantly longer than wild-type worms
PLoSGenetics:February2009|Volume5|Issue2
Sod-2 DELETION IN CAENORHABDITIS
ELEGANS

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EFFECT OF CR AND EXERCISE ON SURVIVAL
IN RATS
Adapted and modified from Holloszy 1995
ClinicalInterventionsinAging2007:2(4)537–543
Median lifespan is increased with Calorie restriction

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Credit:UniversityofWisconsin-Madison/JeffMiller CALORIC RESTRICTION IN MONKEYS
Caloric restriction slows ageing in monkeys

25. Resveratrol (3,5,4‟-trihydroxystilbene) mimics the effects
of dietary restriction
• Hypothesized to activate Sir2, or SIRT1 in
mammals
• Alternatively, hypothesized to upregulate AMPK,
downregulate mTOR (Mammalian target of
rapamycin)
Baur et al. 2006 Nature

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ENHANCING ENERGY EXPENDITURE AND FAT
METABOLISM
Red grape (resveratrol) compound shows promise
Industry looking for exercise mimetics now!
www.medindia.net/news/tripepperblend

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Basic
Functional
PrescriptiveCarbohydrates
Fats
Proteins
Vitamins
Minerals
Water
Flavonoids
Omega 3& 6
Hunger
Satiety
Basic functions
Driven by Cultural
& Ethnic Preferences
Preventive
Performance
Maintenance
Specific needs
For a condition
Driven by
Aspirational
needs
IndulgenceFunction
Doctor
Age
Sustenance Enjoyment / Health Health & Wellbeing
Well-being/
appearance
Age
Add life to
years
Evolution of Nutrition
Deva Kumari, Yashwanth Radhakrishnan & Navin Sharma (2012): International J of Life Science & Pharma
Res. 2(3):174-184

28. Agriculture
Life
Sciences
Forestry
Nutrition
Actives
How to improve nutrition of people in Developing World
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Epigenetics
Human Genome
• New ways of working
• Newer / different alliances and partnerships
• Local knowledge
Focus in-and out-of-RDA

29. Barley Max Odorless Soy RS in Wheat
Amaranth Moringa
Agroforestry – Complete Nutrition
Nutrition Pyramid
29Methionine and Nyacin rich fruits: Peach, Jackfruit, Tamarind, Dates

30. Synsepalum dulcificum, a West African berry better
known as "miracle fruit," changes the way foods taste.
Possible model for the taste-modifying activity of MCL. (A) MCL is held on hT1R2-
hT1R3 at neutral pH (Left) and activates it under acidic pH (Right).
Koizumi A et al. PNAS
2011;108:16819-16824
MCA= Miraculin
MCL is widely used in Japan, where dedicated cafés are serving low-cal food
with a miracle fruit on the side

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Low GI Palm Sugar

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Low GI Maple Sugar

33. Oil with High Oleic / High Stearic Acid
Margarines and spreads with cardio neutral saturated fatty acid – no chemical
hydrogenation & no trans fats
Enhanced functionality with higher heat stability for frying and improved shelf life

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Amla, or Indian gooseberry (Emblica officinalis),
cultivated in India, has long been used in
Ayurveda.
Fruit contains between 700 and 1,000 mg of
vitamin C. The vitamin C is considered to be
highly stable due to the presence of tannins and
polyphenols.
Additionally, evidence suggests that amla may
help to boost immune response, presumably due
to its vitamin C content
Immunity: Emblica officinalis

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Activating alpha waves in Brain: Theanine
Tea Contains Theaninie and Caffeine
Required Physiological Level – 50mg
Current Level – 20mg
http://www.biomedcentral.com/1471-2164/12/131

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• Nutrilite is the vitamin brand to grow, harvest and process
plants on its own organic farms.
• Controls the development of its supplements from seed to
finished product.
• Claims to practice sustainable farming, the future of
organic farming.
• Owns 4 farms in 3 countries with over 6000 acres. (more
than any other supplement company)
• Established a Nutri-Certification program. This insures
that any plant concentrate purchased has been grown
according to strict organic farming specifications.
Primary crops: blueberry, Echinacea purpurea, Echinacea
angustifolia, oregano, peppermint, nettle, valerian, white
kidney bean, dandelion, lemon balm, black cohosh. spinach,
kale, broccoli, watercress, parsley, grapefruit, orange,
lemon, oregano, sage, and asparagus. acerola; picão preto,
also called Spanish needle, and passion fruit

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Take Home Message
• To maintain normal human functions recommended calories
and RDA of micro + macro nutrients are required
• Nutrition can also enhance certain functions e.g. aging
• Rapid progress in biosciences pointing to altered genome functions by
nutrition
• Specially during pregnancy and early childhood
• A nutrition strategy therefore should consist of meeting RDA
and enhanced function
• Trees can play an important role : healthy carbohydrates and fats