Some people have called NAD+ an  anti-aging miracle drug. In the last post I briefly mentioned that NAD+ is considered a longevity compound. NAD+ and its precursors are key compounds that Dr. David Sinclair focuses on in his lab at Harvard and that he personally takes daily.[1] In this post, I hope to share what NAD+ is, and why you may want to consider boosting your levels.

NAD+ is a vitamin B3 derivative. It is critical to every cell and is required for energy production and cellular repair. Think high-school biology, Krebs cycle and the Electron Transport Chain. NAD+ is necessary for moving electrons around, which allows us to generate the cellular energy of ATP. It allows us to extract cellular energy from carbohydrates, proteins, and fats.

In addition to energy production, NAD+ also turns on multiple longevity genes, especially the sirtuins.  The sirtuin family of genes are regulators of epigenetics. The sirtuins create enzymes that help keep DNA organized so the DNA can function properly. Sirtuins also help in the repair of damaged DNA, reduce inflammation, and help with stress resistance. As we age, our levels of NAD+ decline, and we have a corresponding decrease in sirtuin activity.  Some researchers suspect that replacing and replenishing NAD+ levels may help stem the aging process.

Some of the studied benefits of increasing NAD+ include:

1.  Improved heart health by decreased arterial stiffness and lower blood pressure. [3,4]
2. Improvement of mitochondrial and neuronal health. In an Alzheimers mouse model, NAD supplementation through precursors slowed cognitive decline. [5,6,7]
3. Life span extension in yeast, worms and rodents. [8,9]

You may wonder why many of the longevity studies on NAD+ are in animal models.  Animals have similar genetic and molecular pathways as humans and unlike humans they do not live as long.  A study in humans on longevity could take a century, whereas in animals the study could be done in 3-5 years. 

Most of the studied benefits with NAD+ have been demonstrated using oral precursors since oral NAD+ is not easily absorbed. An alternative delivery system, IV NAD+, has not been studied as thoroughly, though there are many reported benefits, which include improvements in: 

ADHD, 
executive function, 
addiction,
anxiety, 
depression, 
chronic fatigue and 
cognitive decline.

Given the studied and reported benefits, you may wonder how to increase your NAD+.
​We can maintain youthful levels of NAD+ by either:
1. Decreasing use/destruction of NAD+
2. Increasing production or levels of NAD+

NAD+ is consumed primarily by 1. PARPs (in DNA repair) 2. Sirtuins (as discussed above) and 3. CD-38 (to be discussed below). The largest consumer of NAD as we age appears to be CD-38.  CD-38 is a signaling molecule induced by zombie cells or senescent cells from molecules they secrete. If we want to increase our pool of NAD+ by decreasing usage, the primary target should be cd-38 and zombie cells. [10]

To decrease use of NAD+:
1. Minimize cellular stressors. This includes the boring truisms of reducing or eliminating smoking, eating real foods rather than processed, lowering your intake of sugar, getting enough sleep, and stress management.
2. Lower cd-38 levels. This can be accomplished by lowering the number of zombie cells.  The best way to lower the load is through the use of senolytics. Examples of senolytics include supplements like quercetin, fiscetin and curcumin. A promising animal trial at Mayo Clinic showed a significant reduction in zombie cells using a medication called Desatinib  and quercetin. [11]

NAD+ levels can be increased by: 
1. Fasting
2. Exercise
3. IV NAD+ and oral NAD+ precursors: Animal studies have shown that taking precursors can raise blood levels of NAD by 2.7X, [12] and human studies of IV NAD+ show that NAD+ is both safe and readily taken up by tissues. [13]

To bring it all together, NAD+ is important in energy metabolism and DNA repair. With age, our NAD+ levels fall, and we are more prone to age-related diseases.  NAD+ has been shown in humans to reduce the risk of some age-related diseases and in animals to extend their lifespan.  Though I am hoping to see more research in this area, given the low risk, good safety profile, and potential upside, I personally take oral NAD+ precursors and IV NAD.  As always, talk to your doctor before starting any supplements.

Hope you have enjoyed this,

Amy

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!

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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