NAD+ Reversing Aging? Overview of NR and NMN

Mitochondrial oxidative capacity and NAD⁺ biosynthesis are reduced in human sarcopenia across ethnicities

NAD⁺ Content and Its Role in Mitochondria

NMN as potential therapeutic agent for muscle disease

What is Mitochondrial Dysfunction?

NAD: The many benefits of NAD+

OTHER WAYS TO INCREASE NAD+

There are a number of lifestyle changes you can make  to increase NAD+ in you body.

It’s well known that Calorie Restriction  (CR) can extend longevity by 30–50% in many mammals (32)

CR has also been shown to increase NAD+ levels in the body , thru these pathways:

• Lowering blood glucose levels minimizes inflammation, which consumes NAD+.

• The ketone body BHB signals to increase AMPK to produce more NAD+

• Burning Ketones for fuel instead of glucose requires 1/2 as much NAD+

– Ketone bodies mimic the life span extending properties of caloric restriction (veech,2017)

 KETOSIS BOOSTS NAD+

Ketosis is a metabolic state in which fat provides most of the fuel for the body. It occurs when there is limited access to glucose (blood sugar), which is the preferred fuel source for many cells in the body.

Ketosis can occur in many different diet plans whenever carb intake is low, but is most often associated the Ketogenic Diet, as that is a much easier method for restricting carbs (3, 4, 5, 6).

Recent research now shows Ketosis  provides the benefit in life extension, lowering inflammation and boosting NAD+ (3,9).

Intermittent or Periodic Ketosis is also effective at extending lifespan and likely achieves much of the benefit (36,37).

Some research even shows more benefit from a cyclical rather than a full time Ketogenic Diet (71).

Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice (Newman, 2017)

The Red bars in the chart at left show the increased levels of the Ketone Body BHB produced from a cyclical Keto diet, resulting in Increased NAD+ and greatly improved neurological function and health.

EXERCISE THAT BOOSTS NAD+

Researchers are finding that 2-3  short bouts of High Intensity Interval Training  (HIIT) per week is far more effective at lowering inflammation (and increasing NAD+), especially among older adults (55)

Exercise is very effective at boosting AMPK and NAD+, especially when performed at times of low blood glucose levels  ( more about HIIT ).

Short bouts of HIIT accomplishes the goal, while avoiding overtraining from endurance workouts  which increases inflammation and consumes NAD+ (55).

NAD/NR –  Overview

1. Caloric Restriction, Fasting and Nicotinamide Riboside | Anti-Aging | Articles | Magazine
2. First-human-clinical-study-of-ChromaDexs-NIAGEN-nicotinamide-riboside-meets-primary-endpoint
3. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. – PubMed – NCBI
4. The Secret Life of NAD+: An Old Metabolite Controlling New Metabolic Signaling Pathways – 2010
5. NAD+ metabolism in health and disease. – PubMed – NCBI
6. NAD+ and Sirtuins in Aging and Disease – 2014
7. NAD+ Metabolism and the Control of Energy Homeostasis – A Balancing Act between Mitochondria and the Nucleus
8. NAD+ and NADH in brain functions, brain diseases and brain aging. – PubMed – NCBI

NAD/NR – Aging

1. Vitamins and Aging – Pathways to NAD+ Synthesis – 2007
2. A New, Reversible, Cause of Aging | HMS

NAD/NR – Brain Inflammation

1. Treatment of Brain Inflammatory Diseases by Delivering Exosome Encapsulated Anti-inflammatory Drugs From the Nasal Region to the Brain – 2011

NAD/NR – Caloric Restriction

1. Caloric Restriction, Fasting and Nicotinamide Riboside | Anti-Aging | Articles | Magazine
2. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. 2015 – PubMed – NCBI
3. Caloric restriction: from soup to nuts. – PubMed – NCBI
4. Calorie restriction – Wikipedia
5. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. – 2007

NAD/NR – Fibromyalgia

1. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients – 2013

NAD/NR – Intranasal

1. NAD+ and NADH in cellular functions and cell death. – PubMed – NCBI

NAD/NR – Mitochondrial disorders

1. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients – 2013
2. NAD+ Metabolism and the Control of Energy Homeostasis – A Balancing Act between Mitochondria and the Nucleus
3. Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts. – PubMed – NCBI
4. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction – 2008

NAD/NR – Obesity

1. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity – 2012
2. Milk Ingredient Nicotinamide Riboside ‘Helps Prevent Obesity’ And Burns Fat
3. Niagen nicotinamide riboside may reduce obesity-related inflammation

NAD/NR – Oxidative Stress and Reactive Oxygen Species (ROS)

1. Crosstalk between Oxidative Stress and SIRT1 – Impact on the Aging Process – 2013
2. Reactive oxygen species and mitochondria – A nexus of cellular homeostasis – 2015

NAD/NR – Sirtuins

1. Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk + and Urh1:Pnp1:Meu1 Pathways to NAD -2007
2. SIRTUIN 1 AND SIRTUIN 3 – PHYSIOLOGICAL MODULATORS OF METABOLISM – 2012
3. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging – 2013
4. Targeting SIRT1 to improve metabolism – all you need is NAD+? – 2012
5. Role of Sirtuins in Linking Metabolic Syndrome with Depression – 2016