Amy Savagian MD
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My hope with these posts is to empower others.  I  want to share my interests: those things that enthrall me and I think will interest you.  The posts are not meant to give medical advice, but is meant simply to share the information related to health, wellness and longevity that I find fascinating right now. The first four posts starting October 2019 are the foundation for my lifestyle medicine practice.

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Nutrition & Healthspan

11/19/2019

 
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This is the last week of our four part series on how to play hard, work hard, and be fully engaged with family, friends and community for as long as possible. 

As nutrition is one of the key components of longevity, I hoped this post/email would give you compelling data on the best way to eat, but what I have found, is that the most advanced research on nutrition and longevity is not about what types of foods you should or shouldn’t eat. Instead the best research seems to be on  fasting and caloric restriction, neither of which I realize, are very sexy. But the molecular mechanisms that they turn on are pretty amazing. Both signal our cells to clean house (autophagy), stimulate stem cells, change our epigenetics (the expression of our genetic code), change metabolic pathways, turn on longevity genes like the sirtuins, and improve our stress resistance.  [1,2,3,4] Each of these  improvements should help you to play, work and engage longer.

In my practice, I focus mainly on fasting as, honestly, long term caloric restriction (CR) is not sustainable or very fun. Studies like the one conducted in Biosphere 2, which relegated human volunteers for 24 months to severe CR, resulted in cold, irritable people with no sex drive. [5] However, fasting and intermittent fasting seems to hold a lot of promise, and while not appropriate for everyone, the studies are encouraging.

Fasting has specifically been shown to lower the risk of developing cancer, cardiovascular disease, and neurodegenerative disease. [6] Fasting cycles have been shown to work as effectively as chemotherapy in some tumors, and when combined with chemotherapy it appears to enhance the benefits and lower the chemo side-effects. [7] Fasting can also be a very effective way to lower high blood pressure. [8] Fasting has even been shown to improve verbal recall. [9]

A study by de Cabo suggested that eating patterns may play a larger role than diet composition. [10] This finding is particularly interesting given all of the debate around dietary restriction.  There are so many conflicting trials and so much conflicting information in the area of dietary restriction.  Mediterranean, low carb, low fat, paleo, keto, vegan and vegetarian all seem to have studies saying they are the best.  

What is right answer? Evidence suggests that when people stop eating the processed Standard American Diet (SAD) and move to a real foods plan (eating foods devoid of processed and sugary foods), any of these diet styles are an improvement. If we look at the top ten sources of American calories, grain-based desserts like cakes and cookies top the list followed closely by sugary drinks, alcoholic beverages and dairy desserts. [Source: Report of the 2010 Dietary Guidelines Advisory Committee]

Many patients have asked me about the Netflix show, “The Game Changers.” I propose that when we eliminate the processed and sugary foods and move to a real foods plan whether it’s keto, vegetarian, paleo, low fat or otherwise, we will begin to feel and perform better. If you want a balanced, well-considered perspective on “Game Changers” please see the Peter Attia article.

Getting back to longevity, we know there is a link between sugar and inflammation. You already know the painful consequences of inflammation when you overdo it at the gym, but what you may not be aware of is how inflammation impacts your system when you indulge in too much sugar. I generally suggest avoiding sugary foods such as sodas as well as most processed foods, which can be loaded with hidden sugars. Reducing your sugar intake reduces inflammation, which in turn may slow the aging process.

So how can you eat to live your best life? 

1. Eat “real” foods instead of processed. If you are buying things in box or a can, read labels for grams of sugar and check ingredients.  If you want to get deep in the weeds, I have found Rhonda Patrick's SNP analysis helpful in beginning to understand how different dietary and supplement approaches may affect you based on your genetic profile.

2. Intermittent fasting or time restricted eating may be part of a healthy longevity plan. A Stanford oncology trained friend of mine suggests everyone allow at least 12 hours every night between their last food of the night and breakfast. This allows for autophagy or cell cleaning to occur.

3. A good resource for learning more about how to fast is: “The Complete Guide to Fasting.” I also like the documentary “Eat, Fast, Live Longer.”

4. There are also fasting mimicking diets (FMD's). These are often 3-5 day plans that allow you to consume some food but make your body think it is fasting. Valter Longo a prominent researcher in this field has a commercially available plan called Prolon.  In humans, this FMD lowers inflammation markers, improves blood pressure, enhances cognitive performance, increases circulating stem cells by 800% and lowers biomarkers/risk factors for aging, diabetes, cardiovascular disease, and cancer. [11] Each of these improvements should lead to a longer, healthier life.

I personally like the 5 day FMD, Prolon as it has solid research supporting it. I think a five day plan is easy to finish and the perfect amount of time for a re-set.

-Amy





1.Fontana L, Partridge L, Longo V.D. Extending healthy life span—from yeast to humans. Science. 2010; 328: 321-326 
 2 Mattson, W, et al. Flipping the Metabolic Switch: Understanding and Applying Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb; 26(2): 254–268. doi: 10.1002/oby.22065
3.
 Haigis MC, Guarente LP. Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006 Nov 1;20(21):2913-21.
 
4. Madeo F, De Cabo R. Et al. The search for antiaging interventions: from elixirs to fasting regimens. Cell. 2014; 157: 1515-1526.
 5. Walford R.L. Mock D. Verdery R. MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J. Gerontol. A Biol. Sci. Med. Sci. 2002; 57: B211-B224.
 6. Longo V.D. Mattson M.P. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014; 19: 181-192. 
 7. Raffaghello L. Lee C. Safdie F.M. Wei M. Madia F. Bianchi G. Longo V.D. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc. Natl. Acad. Sci. USA. 2008; 105: 8215-8220.
 8. Goldhamer A.C. Lisle D.J. Sultana P. Anderson S.V. Parpia B. Hughes B. Campbell T.C.Medically supervised water-only fasting in the treatment of borderline hypertension. J. Altern. Complement. Med. 2002; 8: 643-650.

9. Madeo F. Et al. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metabolism. 2019; 30: 3: 462-476.E5.
 10. de Cabo et al. Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories. Cell Metabolism, 2018; DOI: 10.1016/j.cmet.2018.08.011

11. Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377). doi: 10.1126/scitranslmed.aai8700.

Other related studies:

Mattson M.P. et al. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc. Natl. Acad. Sci. USA. 2003; 100: 6216-6220

Panda S. et al. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014; 20: 991-1005

Longo, V.D., Panda S. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab. 2016; 23: 1048-1059

Minor R.K. Allard J.S. Younts C.M. Ward T.M., de Cabo R. Dietary interventions to extend life span and health span based on calorie restriction. J. Gerontol. A. Biol. Sci. Med. Sci. 2010; 65: 695-703

Longo et al.  A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.
Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 

Does Sleep Improve Longevity?

11/12/2019

 
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This week, we are exploring the research on sleep and longevity. This is the third in a four-part series on how to play hard, work hard, and be fully engaged with family, friends and community for as long as possible. [Click here to see the first two weeks posts]

For most of us, being fully engaged and productive often comes at the cost of a loss of sleep. In our productivity-driven culture people say they will “sleep when they are dead”, and from what I have read, those people will get their wish more quickly than they may like. Today, I hope to illustrate why getting at least 7 hours of sleep may be the magic pill to improving health, longevity, intelligence, sexuality, productivity, and likeability. 

Last week we talked about how meditation could change the balance of our autonomic nervous system, which is the part of our nervous system we don’t control from that of sympathetic (a.k.a fight or flight) to parasympathetic (a.k.a. rest, healing and digestion) [1,2]. When our sympathetic nervous system is overactivated for days, weeks or months, we experience more stress and our bodies experience more inflammation. [3] Sleep also helps lower sympathetic tone, which may have health benefits.
To help me understand the benefits of sleep better, I looked first to one of the most prolific researchers on sleep, Matt Walker of UC Berkeley. On a recent podcast Dr. Walker said, “If there is one central, common pathway through which we can understand almost all aspects of the deleterious impact of insufficient sleep, it is through the autonomic nervous system, and specifically an excessive leaning on the fight or flight branch of the nervous system.” To put it more simply, if the lack of sleep leads to more fight or flight, then this high sympathetic tone may be part of the reason we see poor sleep associated with poor immune function, heart disease and diabetes to name a few possible side effects. 

So what have the studies shown? From a health perspective, we have seen that adequate sleep lowers the risk of some cancers. [4,5,6]  Sleep also seems important for lowering risk of diabetes [7,8] and maintaining heart health. One study showed that 6 or less hours of sleep led to a 200-300% increased risk of coronary artery calcification. [9]

When considering longevity, PNAS (Proceedings of the National Academy of Sciences) published an article that found limiting sleep to less than 6 hours for 1 week changed the activity of 711 genes or about 3% of the total genome. [10] It found that the sleep reduction down-regulated genes that were associated with healthy immune functioning and up-regulated genes associated with chronic inflammation and tumor production. In other words, <6 hours of sleep predisposes people to chronic inflammation and tumor genesis or inflam-aging.

Some of the more interesting sleep associations I have found includes sexuality, productivity, and likeability. [11,12,13] If we want to be socially engaged, apparently allowing enough sleep is important. One of Dr. Walkers recent studies shows that sleep loss causes social withdrawal and loneliness. Sleep also seems to impact the brain’s ability to encode new information. This has broad implications, but it’s particularly important for students, or anyone wanting to learn new things such as new acquaintances’ names and the elderly, who are at risk for dementia. [14,15,16] 

Sleep is stigmatized as laziness, but from the studies I have read, adequate sleep can actually lead to a healthier, happier you.  Putting it together, sleep seems improve longevity through lowering the likelihood of disease, accidents and decrepitude. Most people need to allow at least 7 hours of sleep nightly. [17] It may be hard to find the time, but from a risk (loss of time) benefit (improved longevity, social engagement, cognitive performance) perspective, I feel the time investment is repaid by the significant benefits.

So you may ask how can I begin to give myself adequate sleep.  Dr. Walker suggests there are three key factors to maintaining a healthy sleep pattern:
1. Regularity: Maintain consistent sleep and rise times.  
2. Darkness: Try to limit screen time and dim home lights the hour before bed. Darkness is needed for melatonin secretion.
3. Cooler room temperatures: Turn down the heat. Your core body temperature is supposed to drop two to three degrees.

I interpret his three keys as ways to help maintain circadian rhythm, which is an internal clock that regulates our sleep/ wake cycle.  
*Blue light simulates morning light, which at night can hurt sleep. So, the timing of your blue light exposure is important. [15,16,17,18,19,20]

*Morning time outside gives your photoreceptors strong circadian cues. 

*In the evenings, research shows it is best to avoid all blue light (phone screens, computers, TVs), but if you need to work on your computers or phone considers using night shift on iPhones or f.lux that can adjust color based on location and time or you can even use the super cool (not really) blue blocking glasses.  [21,22,23,24,25]

*When you are ready for sleep, a quiet room is also important. You may want to consider noise blocking devices such as kokoon or if you have a noisy partner, there is always the “sleep divorce” as popularized recently by Carson Daly.

*There is evidence that meditation can improve sleep. Please see last weeks post for suggestion on meditation apps.  [26]

*Lastly. CBTI (Cognitive Behavioral therapy for insomnia) has shown great efficacy in improving sleep. [27] Apps such as CBTI coach (from the VA, Stanford SOM and the DoD) and Pzziz are both effective and well  researched.

That is it for this week.  Next week, we will talk about what the research really shows us on nutrition and longevity, and what steps you can take towards a healthier, happier you!



1. Koopman, F.A., Stoof, S. P., Straub, R. H. , van Maanen, M. A. , Vervoordeldonk, M. J. , Tak,  P. P. (2011) Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis. Mol Med; 17(9-10): 937–948. Published online 2011 May 20. doi: 10.2119/molmed.2011.00065

2. Amihai, I., Kozhevnikov, M. (2015). The Influence of Buddhist Meditation Traditions on the Autonomic System and Attention. Biomed Res Int. 731579. Published online 2015 Jun 4. doi: 10.1155/2015/731579

3. Bellinger, D.L.1, Lorton, D. (2018). Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)? Int J Mol Sci. 2018 Apr; 19(4): 1188. Published online 2018 Apr 13. doi: 10.3390/ijms19041188
4. Thompson et al., 2011 Colorectal cancer and sleep: Short duration of sleep increases risk of colorectal adenoma. Cancer. Feb 15;117(4):841-7. doi: 10.1002/cncr.25507.
5. Irwin et al., 1994. Sleep deprivation reduces natural killer cells: Partial sleep deprivation reduces natural killer cell activity in humans. Psychosomatic Medicine. 56(6):493–498. 

6. Hakim et al., 2014. Tumors grow more in sleep deprived mice: Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res. Mar 1;74(5):1329-37. doi: 10.1158/0008-5472.CAN-13-3014

7. Knutson et al. 2007. The metabolic consequences of sleep deprivation. Sleep Medicine Reviews. Volume 11, Issue 3, Pages 163-178.. https://doi.org/10.1016/j.smrv.2007.01.002 

8. Sheen et al. 1996. Relationships between sleep quality and glucose regulation in normal humans. American journal of physiology. 01 AUG 1996. https://doi.org/10.1152/ajpendo.1996.271.2.E261 

9.King et al. 2008. Short sleep duration and incident coronary artery calcification. JAMA 300(24):2859-66. doi: 10.1001/jama.2008.867.

10. Möller-Levet CS et al. 2019 Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome. Proc Natl Acad Sci U S A. Mar 19;110(12):E1132-41. doi: 10.1073/pnas.1217154110.

11. Cote et al 2013. Sleep deprivation lowers reactive aggression and testosterone in men. Biological Psychology. Volume 92, Issue 2, February 2013, Pages 249-256. https://doi.org/10.1016/j.biopsycho.2012.09.011

12. Ben Simon, E., Walker, M.P. 2018 Sleep loss causes social withdrawal and loneliness. Nat Commun 9, 3146 doi:10.1038/s41467-018-05377-0

13. Rosekind et al. 2010. The Cost of Poor Sleep: Workplace Productivity Loss and Associated Costs. Journal of Occupational and Environmental Medicine: January 2010 - Volume 52 - Issue 1 - p 91-98. doi: 10.1097/JOM.0b013e3181c78c30.

14. Walker MP. 2008. Sleep-dependent memory processing. Harv Rev Psychiatry. 16(5):287-98. doi: 10.1080/10673220802432517.

15.Walker, MP. 2008. Cognitive consequences of sleep and sleep loss . Sleep Medicine. Volume 9, Supplement 1, September 2008, Pages S29-S34

16. Mander et al. 2013. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nature Neuroscience,. Volume 16, pages 357–364.

17. NSF -https://www.sleepfoundation.org/articles/how-much-sleep-do-we-really-need

18. Shechter et al. 2017. Blocking nocturnal blue light for insomnia: A randomized controlled trial. Journal of Psychiatric Research. Volume 96, Pages 196-202. doi: 10.1016/j.jpsychires.2017.10.015
19. Zimmerman et al. 2019. Neuropsychological Function Response to Nocturnal Blue Light Blockage in Individuals With Symptoms of Insomnia: A Pilot Randomized Controlled Study, Journal of the International Neuropsychological Society, Volume 25, Issue 7, pp. 668-677. 
20. Czeisler CA (2013) Perspective: Casting light on sleep deficiency. Nature 497(7450):S13

21. Cajochen et al. 2011. Evening exposure to a light-emitting diodes (LED)-backlit computer screen affects circadian physiology and cognitive performance. Journal of Applied Physiology. 110(5):1432-8. doi: 10.1152/japplphysiol.00165.2011.
22. Czeisler et al. 2015. Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness. PNAS- Proceedings of the National Academy of Sciences of the United States of America. 112 (4) 1232-1237;
23. Lockley et al. 2003.  High Sensitivity of the Human Circadian Melatonin Rhythm to Resetting by Short Wavelength Light. The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 9, Pages 4502–4505, https://doi.org/10.1210/jc.2003-030570

24.Burkhart et al. 2009 Amber lenses to block blue light and improve sleep: a randomized trial. Chronobiol Int. 2009 Dec;26(8):1602-12. doi: 10.3109/07420520903523719.
25. Van der Lely, S et al. 2015. Blue blocker glasses as a countermeasure for alerting effects of evening light-emitting diode screen exposure in male teenagers. J Adolesc Health. 56(1):113-9. doi: 10.1016/j.jadohealth.2014.08.002

26. Black, D et al. 2015. Mindfulness Meditation and Improvement in Sleep Quality and Daytime Impairment Among Older Adults With Sleep Disturbances A Randomized Clinical Trial. JAMA Internal Medicine. 175(4):494-501. doi:10.1001/jamainternmed.2014.8081

27. Jacobs et al. 2004. Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison.  Arch Intern Med. 2004 Sep 27;164(17):1888-96.

#2 Can Mindfulness Improve Longevity?

11/2/2019

 
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This week, we are talking about  what the research really shows on living better, longer and mindfulness.  This is the second part of a four part series on how to play hard, work hard, and be fully engaged with family, friends and community for as long as possible.

I have read many claims of improved aging with mindfulness but wanted to see the data myself, so I took a deep dive into the literature of mindfulness and this is what I found.

As you  probably know, mindfulness can take many forms. Mindfulness is a catch-all  term,  but what I think is at the heart of mindfulness is taking time out, whether through meditation, prayer or simply alone time. The blue zones research has shown most centenarians practiced some form of mindfulness, and research shows that in any form, the simple act of taking time out allows for stress reduction. [1,2]​

Since most of the mindfulness research has been done on meditation, I will focus on that today. Many studies demonstrate that meditation can change the balance of our autonomic nervous system (the part of our nervous system we don’t control)  from that of fight or flight (sympathetic) to that of rest, healing and digestion (parasympathetic). [3,4]  When our sympathetic nervous system is over activated for days, weeks or months we experience more stress and our bodies experience more inflammation. [5]

This implies that if we increase our parasympathetic tone we can improve on our ability to heal, and if we heal better, we will age better. [6] This is exactly what some studies have shown.  Meditation practices as short as 3-4 minutes have been shown to increase parasympathetic tone, decreasing our sympathetic tone with improvements seen in blood pressure, immune function and digestion. [2] 

The benefits of meditations have also been evaluated by prominent researchers like Clifford Saron of UC Davis and Nobel Prize winner Elizabeth Blackburn.  They evaluated aging through the lens of stress hormones and DNA (telomere length).  Telomeres protect your DNA. They are protective caps at the ends of chromosomes.  As people age, telomeres shorten. Chronic stress has also been associated with faster telomere shortening, but the catch 22 is that as telomeres shorten people age more rapidly.  Short telomeres have been linked to minor inconveniences like wrinkles and gray hair as well as larger issues like alzhiemer’s, some cancers and heart disease. 

Dr. Blackburn has evaluated the effect of meditation on both stress levels and telomere length and found meditation is associated with longer telomere length. A summary of her work published in 2011 states, “Given the pattern of associations… meditation may have salutary effects on telomere length`…”[7] In other words, meditation seems to help maintain telomere length. 

Dr. Saron of UC-Davis has also shown that meditation is associated with a lower level of the stress hormone cortisol and increased activity of telomerase (the enzyme that can lengthen telomeres). [8].  His studies have also shown that meditation may improve working memory and DHEA levels.  DHEA is a hormone that declines with age and is associated with improved cognitive performance. 

From a risk-benefit perspective and given improvements seen in cognitive performance, aging and healing, I suggest a daily mindfulness practice to all of my patients. If you are a mindfulness novice, there are a few easy ways to begin. 


  • 4-7-8 breaths helps to lower stress levels. To perform a 4-7-8 breath you inhale for a count of 4, hold for a count of 7 and exhale for a count of 8.   Dr. Andrew Weill, a father of integrative medicine also uses it to bring on sleep more quickly. 
 
  • Download one of the many apps available that teach mindfulness and meditation. Calm and Headspace are two of the more popular choices.
 
  • Try Waking Up, one of my new favorite apps that teaches mindfulness. Unlike many other mindfulness practices that “present meditation like an ancient executive stress ball… Waking up has the goal of allowing you to discover in the laboratory of your own mind.”

That is it for this week.  Next week, we will talk about what the research really shows us on sleep!

1.Buettner, D. (2012) The Blue Zones: 9 lessons for living longer from the people who've lived the longest (2nd ed.). Washington, D.C. National Geographic.

2. Creswell, David J. (2017). Mindfulness Interventions. Annual Review of Psychology. Vol. 68:491-516 (Volume publication date January 2017). First published online as a Review in Advance on September 28, 2016. https://doi.org/10.1146/annurev-psych-042716-051139
​

3. Koopman, F.A., Stoof, S. P., Straub, R. H. , van Maanen, M. A. , Vervoordeldonk, M. J. , Tak,  P. P. (2011) Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis. Mol Med; 17(9-10): 937–948. Published online 2011 May 20. doi: 10.2119/molmed.2011.00065

4. Amihai, I., Kozhevnikov, M. (2015). The Influence of Buddhist Meditation Traditions on the Autonomic System and Attention. Biomed Res Int. 731579. Published online 2015 Jun 4. doi: 10.1155/2015/731579

5. Bellinger, D.L.1, Lorton, D. (2018). Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)? Int J Mol Sci. 2018 Apr; 19(4): 1188. Published online 2018 Apr 13. doi: 10.3390/ijms19041188

6.Fountain-Zaragoza, S. Prakash, R. S. (2017) Mindfulness Training for Healthy Aging: Impact on Attention, Well-Being, and Inflammation. Front Aging Neurosci. 9: 11. Published online 2017 Feb 3. doi: 10.3389/fnagi.2017.00011

7. Epel, E., Daubenmier, J., Moskowitz, J.T., Folkman, S., Blackburn, E. (2009) Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres.  Ann N Y Acad Sci. doi: 10.1111/j.1749-6632.2009.04414.x

8.Conklin, Q. A., King, B. G., Zanesco, A. P., Lin, J., Hamidi, A. B., Pokorny, J. J., Saron, C. D. (2018). Insight meditation and telomere biology: The effects of intensive retreat and the moderating role of personality. Brain, Behavior, and Immunity, 70, 233–245. 

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