Amy Savagian MD
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Research & Posts

This page is about my current interests and research.  My hope with these posts is to empower others.  I  want to share the research I am engaging with now and 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 are the foundation for my lifestyle medicine practice.

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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. 

#1: How to Maximize Lifestyle for Healthspan & Longevity

10/20/2019

 
As we go into fall, aging is on my mind.  To be specific aging well is on my mind.  I want to continue to play hard, work hard, and be fully engaged with my family, friends and community.   I think most of my patients want something similar too.  

Dan Buettner’s book, “The Blue Zones” has resurfaced as a recent focus of mine.  In his book he evaluates areas with the longest lived people.  The book is based on epidemiologic data, so it lacks precision, but it points to some larger trends. Over the last five years, since finishing residency, I have worked with my patients to help them institute some of the blue zone principles, and I have found four areas leap to the front as strong predictors of health. 

Better than medicine, the top four health influencing factors that I see include: eating well, sleeping well, daily activity and a mindfulness practice (in whatever form that may take). These next four weeks will focus on activity, mindfulness, sleep and nutrition. My goal is to provide you with strong research in each area. We all know to work out, sleep well, eat well and be mindful, but what does that really mean? I hope to take you on a deep dive to learn what the research actually shows and how you can implement each.  This week, I will tackle activity first as I think it is the easiest to implement from a time and emotional perspective. 

​Activity:
Activity in all forms is one of the most important aspects of longevity and health that I discuss with patients.  From the Blue Zones research we know that activity is a major factor in longevity and wellness.    Movement throughout life helps maintain strength, balance, flexibility and health. In fact, the CDC suggests 150-300 minutes per week of moderate activity or 75-150 minutes per week of vigorous activity. [1]

But what does the research actually show? Most people know that exercise reduces risk of metabolic diseases like diabetes and heart disease, but interestingly there was a study in JAMA showing that only 10 minutes a day of exercise could add years to a persons life. [2] And perhaps less newsworthy, but certainly interesting, there was a study published in JACC 2014 that showed runners were far less likely to die of heart disease regardless of BMI or smoking status.[3] Other studies have shown exercise can reduce all-cause mortality by 30-35%,[4] which means that exercise can be an equalizer and promote longevity even if you have habits such as smoking or are overweight.

So now you may be asking, well, I agree with this, but what should I do? The Mayo Clinic published a study in Cell Metabolism showing that high intensity training HIIT (High Intensity Interval Training: 70-85% max heart rate) turns on more longevity genes than does low or moderate intensity training. [5] The intensity does not need to be long. The 7 minute workout group showed that only 7 minutes of HIIT could be an effective workout. [6] HIIT also has been shown to improve cognitive performance releasing proteins such as BDNF (Brain-Derived Neurotrophic Factor) that assists with neuroplasticity.  If patients are capable, I often suggest a minimum of 5 minutes of daily HIIT, a minimum of 5 minutes of daily strength training to maintain muscle mass and and 5 minutes of core to prevent back pain and maintain balance. 

The  7 minute work out is a great option if you have limited time, space or equipment.  If you are interested in the 7 minute workout, the pictograph below links to The New York Times post on the 7 minute workout. The Human Performance Institute has also built a great app walking clients through 7 minute workouts. At the end of the post you can click the image to watch a video explaining it with exercise physiologist Chris Jordan, who developed the program.

I hope you enjoyed the Now this week! Next week we will wade through the research on mindfulness!
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1.CDC 2018 guidelines - https://health.gov/paguidelines/second-edition/pdf/Physical_Activity_Guidelines_2nd_edition.pdf

2. 
Timothy S. Church, MD, MPH, PhD; Conrad P. Earnest, PhD; James S. Skinner, PhD; et al; (2007) Effects of Different Doses of Physical Activity on Cardiorespiratory Fitness Among Sedentary, Overweight or Obese Postmenopausal Women With Elevated Blood Pressure: A Randomized Controlled Trial JAMA. ;297(19):2081-2091  https://jamanetwork.com/journals/jama/fullarticle/1108370

3.
Artero EG, Jackson AS, Sui X, Lee DC, O'Connor DP, Lavie CJ, Church TS, Blair SN. J (2014) Longitudinal algorithms to estimate cardiorespiratory fitness: associations with nonfatal cardiovascular disease and disease-specific mortality.  Am Coll Cardiol. 3;63(21):2289-96. doi: 10.1016/j.jacc.2014.03.008. Epub 2014 Apr 2.
4.  C. D. Reimers, G. Knapp, and A. K. Reimers, (2012) All-cause mortality is decreased by about 30% to 35% in physically active as compared to inactive subjects (Does Physical Activity Increase Life Expectancy? A Review of the Literature 2012.

5.
Robinson MM, Dasari S, Konopka AR. Johnson ML, Manjunatha S, Esponda RR, Carter RE, Lanza IR, Nair KS. (2017) Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metab. 25(3):581-592. doi: 10.1016/j.cmet.2017.02.009.

6. Klika, B; Jordan, C. (2013) HIGH-INTENSITY CIRCUIT TRAINING USING BODY WEIGHT: Maximum Results With Minimal Investment.  ACSM’s Health & Fitness Journal: 17(3): 8-13.
doi: 10.1249/FIT.0b013e31828cb1e8

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