NMN and Ginseng Show Similar Efficacy To Reverse Muscle Aging

Supplementing accelerated aging mice with ginsenoside Rh4 (Rh4) - the active compound in the root ginseng - mitigates muscle aging, lowers oxidative stress, and enhances mitochondria.

Key Points:

Treatment with Rh4 attenuates skeletal muscle structural abnormalities in mice modeling accelerated aging.
Supplementing mice with Rh4 decreases oxidative stress and inflammation in muscle tissue.
Rh4 supplementation enhances mitochondria and activates SIRT1, a longevity-linked protein tied to mitochondrial health.

Muscle aging is perhaps one of the most pervasive debilitating age-related conditions in the world, leading to loss of independence and compromised mobility. And while strength and resistance training is a well-established intervention to delay muscle decline, dietary regimens also heavily influence muscle health. Thus, researchers have honed in on natural products that hold antioxidative and anti-inflammatory properties, as oxidative stress and inflammation are hallmarks of age-related muscle atrophy.

In a pre-proof article published in Phytomedicine, researchers from Northwest University in China found that supplementing mice modeling accelerated aging with ginsenoside Rh4 – a natural active ingredient in ginseng roots – successfully delays skeletal muscle aging. Additionally, Zhu and colleagues showed that Rh4 treatment significantly ameliorated oxidative stress and inflammation while enhancing mitochondrial function. Notably, Rh4 supplementation also boosted the activity of SIRT1, a known modulator of mitochondrial health.

Rh4 Delays Muscle Aging

It’s clear that diets high in quality protein are paramount to repairing and building muscle tissue as we age. However, foods that quench oxidative stress and inflammation are also vital to healthy muscle aging, as both factors drive the structural decline of muscle fibers. Accordingly, Rh4, utilized in traditional Chinese medicine for centuries, fits into this food category and holds great potential in the fight against muscle decline.

Zhu and colleagues explored the muscle-protective effects of Rh4 in mice modeling accelerated aging. Here, mice were first injected with a sugar called D-galactose to induce premature aging via increased oxidative stress. Then, mice were treated with a low, medium, or high dose of Rh4 for six weeks. While untreated mice exhibited disorganized muscle fibers, those that received Rh4 displayed muscle fibers with an orderly structure and proper alignment of connective tissue, demonstrating healthy muscle fibers.

The investigators also looked at Rh4’s effect on the activity of Nrf2 – a key protein that plays a major role in triggering the antioxidant immune response – and COX2 – a mediator of inflammation and oxidative stress. In a dose-dependent manner, Rh4 significantly increased Nrf2 activity and decreased the levels of COX2. Collectively, the findings demonstrate that Rh4 delays muscle aging potentially by regulating inflammation and oxidative stress.

(Zhu et al., 2023 | *Phytomedicine*) **Rh4 improves muscle fiber arrangement, increases antioxidants, and reduces inflammation.** (Top) Age-accelerated mice (D-Gal) exhibit more disordered muscle fibers than mice treated with a low (L-Rh4), medium (M-Rh4), or high (H-Rh4) dose of Rh4. NMN served as the positive control. Treated mice have significantly higher antioxidant (Nrf2) levels and lower oxidative stress/inflammation (COX2) than untreated mice.

RH4 Enhances Mitochondria

Mitochondria, the cellular powerhouses, are another crucial element of healthy muscle aging, as they provide the energy required for proper muscle function. Hence, it’s essential to have a sufficient pool of healthy mitochondria. Scientists have identified the protein SIRT1 as a major contributor to mitochondrial biogenesis – the creation of new mitochondria – so Zhu and colleagues examined whether Rh4 supplementation affected SIRT1 activity.

The investigators found that supplementing prematurely aged mice with Rh4 significantly increased SIRT1 activity in a dose-dependent manner. SIRT1 promotes mitochondrial biogenesis by activating another protein called PGC-1a, so the research team proceeded to measure PGC-1a activity and found that Rh4 boosted PGC-1a, confirming Rh4’s beneficial effect on mitochondria. Taken together, the findings suggest that Rh4 protects against muscle aging by enhancing mitochondrial health.

(Zhu et al., 2023 | *Phytomedicine*) **Rh4 increases SIRT1 and PGC-1a.** Prematurely aged mice treated with a low (L-Rh4) or high (H-Rh4) dose of Rh4 have greater SIRT1 activity than untreated (D-gal) mice. (Right) Mice treated with a high dose of Rh4 exhibit greater PGC-1a activity than untreated mice.

Ginseng: The Root of Healthy Aging

Many studies have established ginseng as a wonder food in the health and wellness space. In addition to being associated with reduced all-cause mortality among Chinese women, studies have shown that the active compounds within ginseng help restore brain health following a stroke, alleviate fatigue in cancer patients, and inhibit the proliferation of breast cancer cells in vitro. Uniquely, research has also shown that combining ginsenosides like Rh4 with NMN, a precursor to the life-preserving molecule NAD+, amplifies NMN’s ability to restore NAD+ in muscle tissue. With this in mind, it would be interesting to see future studies examine the effects of combining NMN and ginseng on muscle function in aged individuals.