Diet, stress, and cellular aging

Diet, stress, and cellular aging Cindy Leung, ScD, MPH UCSF Center for Health and Community

How old do I look? How old do I feel? How would I rate my physical health?

Diet, stress, and cellular aging The telomere effect Stress and telomeres Foods and telomeres Diet patterns and telomeres

Elizabeth Blackburn, PhD President, Salk Institute 2009 Nobel Laureate Elissa Epel, PhD Professor of Psychiatry UCSF

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1400 Rode et al, 2015 Copenhagen study 1200 1000 y = 360.82e 0.1238x R² = 0.97775 Any cancer Cardiovascular Raw Number of Deaths (unadjusted) 800 600 400 200 Death Other causes Unspecified cause death* All-cause mortality Expon. (All-cause mortality) 0 0 1 2 3 4 5 6 7 8 9 10 Telomere Length decile; 1 = longest; 10 = shortest

Short telomeres and disease Cardiovascular disease (Myocardial Infarction) Diabetes Cancers Dementia (Vascular, Alzheimers) Obesity Insulin resistance Osteoporosis Rheumatoid Arthritis Mortality Samani et al, Lancet, 2001; Brouilette et al, 2003; Arterioscler Thromb Vasc Biol 2003; Sampson, 2006, Diabetes Care; von Zglinicki, 2000, Lab Invest. Jeanclos et al, 2000, Hypertension; Valdes et al,. Lancet 2005; Gardner, 2005, Circulation; Konig, 2006; Cawthon, 2003, Lancet.

Diet, stress, and cellular aging The telomere effect Stress and telomeres Foods and telomeres Diet patterns and telomeres

PBMC Telomere length Av e ra ge t/s ra tio TL is related to high perceived stress 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 Hi g h s tre s s L o w s tre s s Epel ES et al. PNAS 2004 Telomeres in the lowest and highest stress quartiles of the whole sample are compared. controlling for age and body mass index: F(3,27) = 12.8, p <.001

Caregiving Stress & Telomere Length Epel et al. (2004) Damjanovic et al. (2007)

What s on your mind? Do your telomeres care? Stress Perceived stress (Epel et al, 2004; Parks et al, 2009; Puterman 2010) Caregiver stress (Damjanovic, 2006; O Donovan, 2011) Intimate partner violence (Humphreys et al, 2011) Discrimination (Chae et al, 2014; Chae et al, 2016) Early childhood adversity (Drury et al 2012; Tyrka et al. 2010) Psychiatric conditions Major Depression (Simon, 2006; Wolkowitz, 2011) Schizophrenia (Kao, 2008; Fernandez-Egea, 2009) Anxiety (Kananen, 2010; Okereke, 2012) PTSD (O Donovan, 2011; Malan, 2011)

Parental factors and early life exposures Maternal stress, nutrition in utero (Entringer, 2012) Maternal weight (Wojicki, unpublished) Prenatal smoking (Theall, in press) Parental education (Needham, 2012)

Telomere length in adults with fetal stress Prenatal stress Comparison group p<.01 d=0.68 Base pair difference: 295 Difference in years of aging: 5 p<.01 d=0.68 Adjusted for: -age -BMI -Birth weight -Early life stress -Maternal bonding -Current stress -Current depression

Stress and aging biology EXPOSURES STRESS AROUSAL ALLOSTATIC LOAD Oxidative Stress Inflammation Insulin resistance Cell aging (Telomeres) Gene Expression

Diet, stress, and cellular aging The telomere effect Stress and telomeres Foods and telomeres Diet patterns and telomeres

Inflammation Oxidative stress Insulin resistance

Sugary beverages and telomeres Examine the associations between sugar-sweetened beverages (SSBs), diet soda, and 100% fruit juice consumption, and leukocyte telomere length in national sample of US adults Cross-sectional analysis of 1999-2002 NHANES data 5309 healthy adults, ages 20-65 years, with complete diet and TL data LTL assay performed at UCSF using PCR method Diet assessed by one 24-hour diet recall and further adjusted using NCI method for usual dietary intake Analyses adjusted for additional sociodemographic and health variables

Sugary beverages and telomeres Sugar-sweetened soda 1.5 Non-carbonated sugarsweetened beverages Diet soda 0.3 0.3 Fruit juice 0.5 Leung CW, Blackburn EH, Epel, ES. Am J Pub Health. 2014. 0 0.5 1 1.5 2 8 oz servings/ day

Sugary beverages and telomeres Multivariateadjusted β 95% CI Sugar-sweetened soda -0010* -0.020, -0.001 Non-carbonated sugarsweetened beverages -0.001-0.030, 0.028 Diet soda -0.001-0.020, 0.018 Fruit juice 0.016-0.001, 0.033 A daily consumption of 8 ounces = 1.9 additional years of aging! A daily consumption of 20 ounces = 4.4 additional years of aging! Leung CW, Blackburn EH, Epel, ES. Am J Pub Health. 2014.

Obese adults had shorter telomeres (-8.8 years of aging) compared to lean adults. Smoking (former/current) associated with -4.6 years of aging. Women moderately or highly active had longer telomeres (+4.4 years of aging) compared to less active women

Sugary beverages and telomeres Take-away points from NHANES: A daily 8-oz serving of soda was associated with shorter telomeres, independent of sociodemographic and health characteristics Magnitude of effect for 20-ounce serving of soda similar to physical activity (in opposite direction) or smoking! Limitations: cross-sectional nature of the data, potential unmeasured confounding by other variables Results suggest telomere length may represent a new link between sugary beverages and metabolic disease

Sugary beverages and telomeres a follow-up Examine the longitudinal between sugary foods and beverages leukocyte telomere length in a pilot study of pregnant women Mindfulness intervention of overweight and obese women to improve gestational weight gain outcomes (n=65) LTL measured at baseline, 3 months and 9 months postpartum Diet assessed by two 24-hour diet recalls at baseline, 32-34 weeks gestation, and 9 months postpartum

Average servings consumed Sugary beverages and telomeres a follow-up 1.4 1.2 1 0.8 0.6 0.4 0.2 0 Dairy desserts Yogurt Baked goods Candy Syrups Sugary Baseline 32-34 wk 9 months PP beverages Leung CW, Adler NE. Eur J Clin Nutr. 2016.

Sugary beverages and telomeres a follow-up Changes in LTL z-score in relation to concurrent changes in foods/beverages from baseline to 9 months PP β* 95% CI Dairy desserts 0.109-0.087, 0.306 Yogurt -0.442-1.334, 0.451 Baked goods -0.021-0.069, 0.027 Candy 0.133-0.147, 0.413 Syrups and sweet sauces -0.017-0.079, 0.045 Sugary beverages -0.102* -0.192, -0.013 *Estimates adjusted for age, race/ethnicity, education, prepregnancy BMI, and concurrent changes in diet quality, smoking, and physical activity Leung CW, Adler NE. Eur J Clin Nutr. 2016.

Sugary beverages and telomeres a follow-up Take-away points from NHANES: Changes in sugary food consumption was not associated with changes in LTL Reducing SSB consumption during prenatal and postpartum periods associated with longer LTL, independent of other health behaviors Limitations: sample size First longitudinal study to show reductions in SSB consumption are reflected in longer LTL; larger observational studies needed for confirmation

More foods and LTL Foods Associated with Shorter Telomeres Foods Associated with Longer Telomeres

Diet, stress, and cellular aging The telomere effect Stress and telomeres Foods and telomeres Diet patterns and telomeres

Why study diet patterns? Represent combined effects of all foods consumed in a person s diet Dietary behaviors are correlated! Dietary factor related to disease might be proxy for unmeasured dietary factor commonly found in diet pattern observed Food should be viewed as a whole, integrated system, and not merely as a collection of individual nutrients and other bioactive substances. Jacobs and Tapsell 2007

Diet Quality Indices Based on Current Knowledge Healthy Eating Index (HEI)-2010 Measures adherence to the 2010 Dietary Guidelines, developed by USDA Scores awarded for higher intakes of total fruit, whole fruit, total vegetables (incl. white potatoes), greens and beans, whole grains, dairy, total protein foods, seafood and plant proteins, fatty acids Scores awarded for lower intakes of refined grains, sodium, and empty calories Alternate Healthy Eating Index (AHEI)-2010 Based on foods and nutrients predictive of chronic disease risk, developed by Harvard researchers Scores awarded for higher intakes of vegetables (excl. white potatoes), fruit, whole grains, nuts and legumes, long-chain fats, polyunsaturated fats, and moderate alcohol Scores awarded for lower intakes of sugary beverages/ fruit juice, red/processed meats, trans fat, and sodium Mediterranean Diet Score Measures adherence to the Mediterranean diet Scores awarded for higher intakes of whole grains, fruits, vegetables, white potatoes, legumes, fish, and olive oil Scores awarded for lower intakes of red meat, poultry, and full-fat dairy Dietary Approaches to Stopping Hypertension (DASH) Based on foods and nutrients predictive of hypertension Scores awarded for higher intakes of fruits, vegetables (excl. white potatoes), nuts and legumes, whole grains, and low-fat dairy Scores awarded for lower intakes of sodium, red and processed meats, and sugary beverages

Diet patterns and telomeres Examine evidence-based healthful diet patterns in relation to leukocyte telomere length in a national sample of US adults Cross-sectional analysis of 1999-2002 NHANES data 4758 healthy adults, ages 20-65 years, with complete diet and TL data LTL assay performed at UCSF using PCR method Diet assessed by one 24-hour diet recall Analyses adjusted for additional sociodemographic and health variables

Diet patterns and telomeres HEI-2010 AHEI-2010 DASH index MedDiet score HEI-2010 1.0 AHEI-2010 0.61 1.0 DASH index 0.65 0.73 1.0 MedDiet score 0.51 0.62 0.58 1.0

Diet patterns and telomeres 120 100 80 60 40 20 0 HEI-2010 AHEI-2010 DASH MedDiet All Men Women Max

Diet patterns and telomeres Standardized diet pattern scores All adults Men Women β 95% CI β 95% CI β 95% CI HEI-2010 score 0.015 0.003, 0.028 0.007-0.007, 0.021 0.024 0.008, 0.039 AHEI-2010 score 0.009-0.000, 0.018-0.002-0.015, 0.012 0.019 0.007, 0.031 DASH index score 0.016 0.003, 0.029 0.012-0.002, 0.027 0.019 0.003, 0.035 MedDiet score 0.009 0.000, 0.018 0.002-0.011, 0.015 0.017 0.005, 0.029 *Estimates adjusted for age, sex (except sex-stratified models), race/ethnicity, education, marital status, household income, alcohol intake, smoking status, pack-years of smoking, physical activity, total energy intake Leung CW, Epel, ES. In prep.

Diet patterns and telomeres Take-away points from NHANES: Multiple healthful patterns related to longer LTL Battle of the scores did not show one pattern stronger Healthful patterns share components of being high in fruits, vegetables, whole grains, plant-based proteins, and low in red// processed meats, sodium, and added sugars Limitations: cross-sectional nature of the data, potential unmeasured confounding by other variables Focus on overall diet quality and not on individual foods or nutrients for optimal health and longevity!

To protect your telomeres

Acknowledgments UC San Francisco Elissa Epel Nancy Adler Elizabeth Blackburn Jue Lin Kim Coleman-Phox Claire McEnvoy AME lab UC Berkeley Barbara Laraia Other collaborators Teresa Fung (Harvard) David Rehkopf (Stanford) Belinda Needham (Michigan) Funders Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute of Aging (NIA)