Harder, Better, Faster, Stronger: NMN Helps Preserve Muscles in Old Age

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man running; Harder, Better, Faster, Stronger: NMN Helps Preserve Muscles in Old Age

As we age, muscle fibers crumble, muscles erode, and motor skills fade, contributing to a diminished quality of life. But how the process of aging affects muscle mass and function within the body has eluded researchers. That’s likely why there currently aren’t practical diagnostic methods or treatments to counter the age-related decline of muscle tissue.

Not too long ago, research from the Department of Neurology at Harvard Medical School showed that mutations in the mitochondria, the cell’s power-generating structures, drives accelerated muscle deterioration, which they were able to mitigate with a supplement called nicotinamide mononucleotide (NMN). This work offers a possible avenue of treatment for preventing age-related loss of muscle function.

NMN Boosts Energy Production and Age-Related Declines in Function

Research has shown that optimizing cellular energy production is helpful when trying to improve the performance of different tissues in the body. The mitochondria powers cells through a series of biochemical reactions collectively known as oxidative phosphorylation. For these reactions to work, cells need to have an abundant and steady supply of NAD+, a compound that provides the building blocks for ATP — the actual fuel that cells run on.

Unfortunately, NAD+ availability decreases with age and in certain chronic diseases. This creates a strain on energy production, and as a result, tissues become compromised and dysfunctional. Previous studies have shown that supplementing with NMN, a precursor to NAD+, is a safe and effective way of compensating for the age-associated decline in energy production (1).

NMN has also been shown to have powerful anti-aging properties. Studies show that supplementing with NMN can improve chronic conditions like obesity, insulin resistance, and muscle dysfunction (2). From worms to flies to rodents, supplementing with NMN has been shown to extend the lifespan of several types of animals (3). Scientists believe that NMN’s anti-aging properties work by improving energy production and optimizing different biological pathways.

arm and back muscle anatomy; dysfunction of the mitochondria, the cell’s power-generating structures, drive accelerated muscle deterioration

Rescuing Muscle Function with NMN

Researchers from Harvard Medical School designed a study to examine the effects of NMN supplementation in an animal model of muscle aging (4).  To do so, they had to develop a new type of assessment to quantify overall muscle state and function, which they used to examine mice that carried a special mutation that alters mitochondrial DNA and causes typical aging-associated features. 

The test, called electrical impedance myography (EIM), uses an electrical current that is passed through muscle fibers that can pick up on any alterations in muscle condition, such as fat deposition and connective tissue changes. EIM provides a major improvement over the current strategies to assess muscle health, like measurements of the hand’s grip strength or questionnaires. EIM allows for the evaluation of parameters directly related to age-related muscle decline at the cellular level.

The mice used in the study were genetically modified to carry a mutation that accelerates aging — as well as weight reduction, osteoporosis, enlargement of the heart, and muscle deterioration — by causing mitochondrial dysfunction. These genetically altered mice, as well as regular mice not carrying the mutation, received NMN supplementation for 20 weeks.

The EIM tests showed that although all mice lost muscle mass as they got older, the loss was greater and happened faster in the mice with the mutation that causes mitochondrial dysfunction. However, when these mice received NMN supplementation, up to 50% of their muscle mass was conserved compared to the untreated groups. Also, mice without the mutation saw beneficial effects in muscle mass when treated with NMN compared to their untreated counterparts.

These findings are in line with other studies that show that supplementing with NMN helps compensate for the decrease in NAD+ availability that happens as part of the aging process. This therapy prevented the loss of muscle mass in the treated mice by enhancing mitochondrial oxidative metabolism. These effects of NMN highlight the preventive and therapeutic potential of NMN as an effective anti-aging intervention that could help preserve mobility and quality of life in humans.

Show references
  1. Gariani K, Menzies KJ, Ryu D, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology. 2016;63(4):1190-1204. doi:10.1002/hep.28245
  2. Irie J, Itoh H. Aging and homeostasis. Age-associated diseases and clinical application of NMN(Nicotinamide Mononucleotide). Clin Calcium. 2017;27(7):983-990.
  3. Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013;154(2):430-441. doi:10.1016/j.cell.2013.06.016
  4. Clark-Matott J, Nagy JA, Sanchez B, et al. Altered muscle electrical tissue properties in a mouse model of premature aging. Muscle Nerve. 2019;60(6):801-810. doi:10.1002/mus.26714

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