Telomere Science

1. Telomere Science Susie Rockway, Ph.D, C.N.S. David Despain, MS

2. Outline • Define Telomeres • What are the issues? • Provide overview of key epidemiological studies associating lifestyle and dietary factors with telomere length • Life Style factors: • Body weight (obesity) • Exercise • Stress • Dietary factors • Vitamins and vitamin D • Fish oil (Omega-3 fatty acids—EPA and DHA) • Dietary fiber (insoluble) • Green Tea

3. Telomeres: what are they? The end of chromosomes (DNA sequences with base pairs TTAGGG) that protect DNA They shorten with cell division (natural aging process) Highly sensitive to oxidative damage (more so than DNA ) Other things besides “aging” can accelerate the telomere shortening Enzyme (telomerase) adds base pairs (bp) to keep telomeres from getting too short Telomere length is emerging as novel marker of biological age (vs chronological age) The BUZZ: product B stimulates telomerase, reduces telomere shortening (maybe even lengthen), therefore we are may extend life—cannot say this! But they are thinking it

4. Telomere Length: a biomarker "Telomere length, like any other risk measurement, tells us the probability of disease and early mortality. It is not a diagnosis," Dr. ElissaEpel, a health psychologist at the University of California-San Francisco and a founder of Telomere Health Inc., one of the companies that tests telomere length—part of the Elizabeth Blackburn’s group Studies I will show you are OBSERVATIONAL associating telomere length with some health aspect...these studies were not designed to test “cause and effects”—ideal type of study: i.e.”1000 mg Vitamin D taken daily for three years showed increased telomere length in women compared to women not taking vitamin D”.

5. Some studies associating telomere length with morbidity and mortality Epel et al. The rate of leukocyte telomere shortening predicts mortality from CVD in elderly men. Aging. 2008;1(1):81-88. Cawthon et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003; 361(9355):393-395. Brouilette et al. White cell telomere length and risk of premature myocardial infarction. ArteriosclerThrombVasc Biol. 2003;23(5):842-846.

6. Protecting telomers • Outcome desired using Isagenix: Protect telomeres or reduce “accelerated telomere shortening” • Will we ever measure telomeres? You can...takes a while to see a difference (years) • The HOPE: if I “protect” my telomeres from shortening, I live longer? A stretch for sure, but its probably the conclusion people will jump to...what are we responsible for? • So, what can we say ?

7. Why talk about telomeres? Q: If they are a “marker” for biological aging, who cares??? We can’t really measure them to show we did something, then why talk about them? A: Use the literature! • Scientific studies are showing associations with diets and lifestyle, so perhaps we can link to these and suggest our products with lifestyle changes may also protect telomeres • AND a potential side-affects, you may feel younger!

8. Delima • What do we wish to tell our associates? • What product(s) do we wish to implicate with telomeres? • Can we substantiate any product with telomeres? • Can we defend “lifestyle” habits that may impact telomeres or Happy Aging? Healthy Aging? • What is our moral and ethical decision in selling products if we don’t have substantiation?

9. What existing data can we link to? How do any of our • Products (Product B?) • Programs (30-day?) • ingredients (vitamins, Coq-10?) relate to published literature?

10. Lifestyles Associated with Telomere Length

11. Those with longer courses of major depression had significantly shorter leukocyte telomeres than controls. This was research led by Elizabeth Blackburn Wolkowitz et al. Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings. PLos One. 2011 18 participants diagnosed with Major Depressive disorders were analyzed for life history, LTL and inflammatory markers

12. Activity level and lifestyle correlated with telomere length 2,401 white twin volunteers answered questionnaires regarding their physical activity level over the previous 12 months.. Subjects who exercised ~ 200 minutes per week (~ 30 min/day) had longer telomeres (200 nucleotides longer) than those who exercised less than 16 minutes per week Cherkas L et al. The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length. Arch Intern Med. 2008;168(2):154-158.

13. A cross sectional study in 647 women ages 35 to 74 • Higher BMI (ages 31 to 39) • Weight gain • Weight cycling • Inversely associated with leukocyte telomere length Kim S et al. Obesity and weight gain in adulthood and telomere length. Cancer Epidemiology Biomarkers & Prevention 2009; 18: 816-20.

14. Dietary Factors that may impact telomeres • Epidemiologic evidence that multivitamin use was associated with longer telomere length among women

15. Regular multivitamin use  associated with longer telomeres National Institute of Health published these epidemiological data AJCN, 2009 The study found that women who used multivitamins had an average of 5 percent longer telomeres compared to non-users of multivitamins This may be translated to nearly a decade of age-related telomere loss

16. Middle vit. D tertile Lowest vit. D tertile Highest vit. D Richards JB et al.Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J ClinNutr 2007; 86: 1420-5. Blood collected in 2,160 women Results: high CRP (oxidative stress) had shortest telomeres; high CRP and low Vitamin D had shortest telomeres

17. Vitamin D: In the large population of women higher serum vitamin D concentrations were associated with longer LTL Every tertile of vitamin D, LTL was shorter in individuals with higher CRP concentrations associated with 5 y of chronologic age Although these associations do not prove causality, they do suggest that vitamin D may play an important role in the modulation of LTL, which is related to aging and age-related diseases. Shortened LTL is an independent risk factor for coronary heart disease and our results suggest that vitamin D, which is easily modifiable through supplementation, may possibly attenuate LTL degradation. Vitamin D supplement users were also found to have longer LTLs than did nonusers, which provides support for this hypothesis.

18. Fish oil: omega-3 fatty acids Patients with coronary artery disease– were followed for 5 years Divided into quintiles based on blood omega 3 levels Those in the lowest quartile of DHA / EPA experienced the fastest rate of telomere shortening over 5 years those in the highest quartile experienced the slowest rate of telomere shortening Each 1-SD increase in DHA_EPA levels was associated with a 32% reduction in the odds of telomere shortening Conclusion : Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening JAMA. 2010

19. Fish oil and Telomeres: • This study did not supplement subjects with omega-3 • This was an observational study • This population had heart disease • In science thinking, you can’t jump from a “diseased population” and suggest these data apply to a healthy population—gotta test the healthy population! • So, can we say?: “High blood levels of omega-3 fatty acids may reduce the rate of telomere shortening”

20. Dietary Fiber Dietary fiber intake was positively associated with telomere length Polyunsaturated was associated with telomere length (PUFA’s may be inflammatory) Waist circumference was inversely associated with telomere length They found no association between telomere length and smoking, physical activity, or postmenopausal hormone use. ??

21. Cross sectional study from 2,284 women in the Nurse’s Health Study Women with the highest intake of whole grains, insoluble fibers and Vitamin E had the longest telomeres Higher BMI, high fat diets and diets high in Omega-6 fatty acids correlated with a shorter LTLCassidy A et al. Associations between diet, lifestyle factors, and telomere length in women. AJCN 2010

22. Green Tea Drinking more than 3 cups of green tea daily is associated with longer telomere length in elderly Chinese men, according to researchers from the Centre for Nutritional Studies, Chinese University of Hong Kong. The study was published in 2010 in the British Journal of Nutrition. The men with the highest tea consumption -- more than three cups or 750 ml per day -- had a telomere length that corresponded to a difference of five years of life.

23. Lets discuss!!!