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Nutrition Beyond Calories & the Role Trees can play

Navin SharmaScience 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

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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

7Source: 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)

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 withzinc

methioninecholinefolateB12

• 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

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SMother’s nutrition and epigenetic changes

"Genetic Science Learning Center, University of Utah, http://learn.genetics.utah.edu."

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

12Changes in gene expression, cellular memory, reversible, no change in DNA structure

Homeostasis Broken Down with methylation

Disease : Outcome of interaction of DNA and Food components

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.0073097http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073097

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Nutrient or diet Epigenetic mechanismEmbryonic development Folate DNA methylation, imprinting

Choline DNA methylation

Protein restrictionDNA methylation, histone modifications

Alcohol DNA methylation

Stem cell ButyrateHistone acetylation, DNA methylation

Retinoic acid PRCAging Folate DNA methylation

Calorie restriction Histone acetylationImmune function Folate DNA methylation

Cancer Methyl-deficient dietHistone modification, microRNA

Genistein DNA methylation, microRNA

(−)-Epigallocatechin-3-gallate DNA methylation, PRC

Curcumin microRNAObesity, insulin resistance High-fat diet DNA methylation, microRNA

Methyl-deficient diet DNA methylation

Curcumin Histone acetylationInflammation Resveratrol Histone acetylation

AdoMet Histone methylation

Methyl-deficient diet microRNA

Neurocognition CholineDNA methylation, histone methylation

16Add 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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Increase in SOD may act as a determinant in longevity

ANTIOXIDANTS AND AGEING

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MLSP- Maximum lifespan potential

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ANTIOXIDANTS AND LIFESPAN

Increased concentration of antioxidants help in longevity

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19Sod 2 null mutants show decreased life span in Drosophila

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A Sod2 NULL MUTATION IN DROSOPHILA

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).

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21SOD 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!!

22sod-2 mutant worms live significantly longer than wild-type worms

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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

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Median lifespan is increased with Calorie restriction

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CALORIC RESTRICTION IN MONKEYS

Caloric restriction slows ageing in monkeys

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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Basi

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CarbohydratesFatsProteinsVitaminsMineralsWater

FlavonoidsOmega 3& 6

Hunger SatietyBasic functions

Driven by Cultural& Ethnic Preferences

PreventivePerformanceMaintenance

Specific needs For a condition

Driven by Aspirationalneeds

Ind

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Fun

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DoctorAge

Sustenance Enjoyment / Health Health & Wellbeing

Wel

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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

Agriculture

Life SciencesForestry

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

Barley Max Odorless Soy RS in Wheat

Amaranth Moringa

Agroforestry – Complete NutritionNutrition Pyramid

29Methionine and Nyacin rich fruits: Peach, Jackfruit, Tamarind, Dates

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

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 CaffeineRequired Physiological Level – 50mgCurrent 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