Dr. Elissa Epel on Telomeres and the Role of Stress Biology in Cellular Aging

Dr. Alyssa Epel

• Dr. Alyssa Epel is the director of the Aging, Metabolism, and Emotions Center and a professor of psychiatry at the University of California, San Francisco.
• Her research focuses on how stress impacts the aging process.

Aging Process

• Aging can be looked at in terms of lifespan (how long people live), healthspan (how long they live without chronic diseases), and cellular aging.
• Aging biology is elastic, meaning it can vary greatly between individuals.
• The goal is to focus on increasing healthspan, or years of healthy living, rather than just increasing lifespan.

Telomeres

• Telomeres are the protective caps at the ends of chromosomes that protect the genome from damage.
• They get worn down with age and stress, and their length can be an indicator of cellular aging.
• Telomerase is an enzyme that can rebuild telomeres, but its activity varies between cell types and individuals.
• In general, longer telomeres are better, but there is a complex relationship between telomere length, telomerase activity, and aging.

Aging and Lifestyle

• A healthy lifestyle, including activity, nutrition, and stress management, can slow down the aging process and increase healthspan.
• Positive stress, social connections, and support are also important predictors of longevity.
• Telomere length and telomerase activity can be influenced by lifestyle factors, such as metabolic health and socioeconomic circumstances.
  Telomeres and Aging
• Telomeres: protective caps on the ends of chromosomes 
  • Shorten with each cell division, eventually leading to cell death
  • Longer telomeres associated with less heart disease, metabolic disease, and lower risk of degenerative diseases like dementia
  • However, extremely long telomeres can increase the risk of certain cancers (e.g., glioma, melanoma)
• Rodents have long telomeres but short lifespans 
  • Not a great model for humans, as they don’t die of short telomeres unless genetically manipulated
• Genetic disorders with shortened telomeres can cause early aging 
  • Can be transmitted to offspring, leading to mild aging syndromes

Environmental Factors Affecting Telomeres

• Exposome: all factors outside of our skin that affect us 
  • Poor neighborhood, poor diet, psychological stress, chemical exposure, etc.
  • All related to shorter telomeres
• Chemical exposure (e.g., BPA, Roundup, heavy metals) linked to inflammation and telomere shortening 
  • National Institute of Environmental Health interested in using telomeres as an index of exposures
• Psychological stress (e.g., unsafe neighborhood, traumatic experiences) can leave an imprint on telomeres, especially in youth 
• Nutrition and telomere length 
  • Whole foods, healthy diet related to longer telomeres
  • Pro-​​inflammatory foods (e.g., red meat, processed meat, sugared drinks, high sugar foods) related to shorter telomeres
  • Coffee associated with longer telomeres

Sugar-​​Sweetened Beverages and Telomeres

• Drinking sugared beverages linked to accelerated telomere shortening and increased biological age 
  • Liquid sugar causes a significant metabolic disturbance
  • One of the biggest predictors of obesity and diabetes
• Sugar addiction
  • Activates dopamine and reward pathways in the brain, similar to some recreational drugs
  • Difficult to control, leading to an obesity epidemic

Addressing the Root Cause of Health Issues

• Medications can extend life by preventing heart attacks or strokes, but don’t address the underlying problem (e.g., unhealthy diet, psychological stress) 
  • Quality of life not improved if the root cause isn’t addressed
• Metformin as an example 
  • Slows aging, but does little if the person is still consuming a lot of sugar
  • Need breakthroughs to slow aging, but must be done in conjunction with a healthy lifestyle

Interventions to Slow Aging

• Psychological stress and telomere length 
  • Toxic stress (e.g., trauma, chronic stress) leads to shorter telomeres
  • Positive stress (e.g., healthy challenges, supportive relationships) can buffer negative effects and promote longer telomeres
    Telomere Shortening and Chronic Stress
• Chronic stress, not short-​​term stress, is related to telomere shortening 
• Rumination, or constantly thinking about something, is part of chronic stress
• Meditation can help reduce rumination and promote presence

Daily Stress and Accelerated Aging

• People with elevated perseverative cognition or thought processes have accelerated biomarkers of aging, such as telomere length and inflammation
• Waking up in a stress state, feeling anxious, and worrying can contribute to accelerated aging
• Caregivers often experience higher stress levels upon waking up

Pessimism vs Optimism

• Pessimism is related to shorter telomeres
• Being aware of one’s pessimistic tendencies can help diffuse their power
• Exercise can help reduce ruminative processes and alleviate pessimistic thoughts

Sex Differences in Aging

• Women generally live longer than men, but the reasons for this are not fully understood
• Estrogen is thought to be protective and anti-​​aging, improving mitochondrial health and upregulating telomerase
• Women have longer telomeres than men, starting at birth

Pregnancy, Stress, and Telomeres

• Stress during pregnancy is associated with shorter telomeres in cord blood
• The health of both the mother and father before conception can impact the health of the baby through epigenetics
• Maintaining a healthy lifestyle, including good nutrition, exercise, and stress management, is important for both parents before and during pregnancy
  Sperm DNA and Obesity
• Over 500 genes’ expression changed in obese men’s sperm DNA compared to non-​​obese men 
  • Many genes related to metabolism and cognitive function
• Bariatric surgery in morbidly obese men led to sperm DNA epigenetics returning closer to lean men’s sperm DNA
• Animal studies show that obese male mice have offspring with health issues, such as type 1 diabetes

Telomere Length in Sperm Cells

• Older fathers have sperm with longer telomeres
• Longer telomere length in sperm can affect offspring’s telomere length to be longer
• Telomere length at birth is a significant determinant of telomere length in late life

Lifestyle Factors Affecting Telomeres

• Omega‑3 supplements and higher blood levels of omega‑3 positively correlate with longer telomeres
• Vitamin D levels in the range of 40–60 nanograms per milliliter are associated with better telomere health
• Exercise, weight loss, and stress reduction can lead to telomere lengthening
• Inflammation and metabolic health play a significant role in telomere length and overall health
  Continuous Glucose Monitors and Personalized Diets
• Continuous glucose monitors can help determine individual responses to different foods 
• Study by the Weitzman Institute: 
  • 800 people with continuous glucose monitors
  • Given various foods (simple sugars, complex carbohydrates, high-​​fat foods)
  • Genetic variations and microbiome data analyzed
  • People had different blood glucose responses based on genetics and microbiome
  • Fiber consistently lowered glucose response

Gut Health, Microbiome, and Telomeres

• Inflammatory processes in the gut can be linked to psychological stress
• Corticotropin-​​releasing hormone activates macrophages in the gut, causing inflammation
• Inflammation can lead to activated immune cells, potentially affecting telomere length
• Research on the link between leaky gut, microbiome, and telomere length is ongoing

Healthy Habits for Longer Telomeres

• Healthy diet (cutting out processed foods, simple sugars, processed meats)
• Exercise (even just 10 minutes of vigorous walking per day)
• Meditation (find a type that works for you)
• High-​​stress caregivers with shorter telomeres benefited from being active
• Extreme sports and marathon runners have slightly longer telomeres, but not much longer than those who exercise moderately

Intermittent Fasting and Telomeres

• No studies have been done on the link between intermittent fasting and telomere length yet

Meditation and Telomere Length

• Study on a 3‑week meditation retreat showed potential benefits for telomere length, especially for those with a tendency for negative emotions
• Different types of meditation work for different people (e.g., yoga, long runs)

Measuring Biomarkers of Aging

• Consumer-​​available tests for biomarkers of aging are limited
• Accuracy of tests that measure telomere length is uncertain
  Telomere Testing
• Telomere testing can be interesting, but should be taken with a grain of salt 
  • Important to be educated on the accuracy and meaning of the test results
  • Population-​​based studies inform risk, not individual tests
• Monitoring telomere length over time may be more useful 
  • Long telomeres shorten faster, short telomeres are more stable
  • Significant changes in short telomeres may not be a good sign
• Technical issues can affect test results 
  • Blood samples may be exposed to oxidative stress during shipping
• Dr. Elissa Epel and Dr. Elizabeth Blackburn have written about telomere testing 
  • Their website, Amecenter UCSF, provides information on testing labs, pros, and cons
  • They also co-​​authored a book called “The Telomere Effect”

Resources

• Amecenter UCSF: Website
• The Telomere Effect: Book
• Dr. Elissa Epel: Twitter