Highlights

  • Sirtuins are enzymes fueled by NAD+ (nicotinamide adenine dinucleotide), associated with advantageously modulating aging. 
  • The GLP-1 receptor agonist drug liraglutide was shown to reduce inflammation and improve bone health via sirtuin 1, the most well-studied sirtuin. 
  • Combining NAD+ boosters with sirtuin activators could provide additive and synergetic effects.

The weight loss drug Ozempic has been shown to reduce its user’s death rates, qualifying it as a longevity (living longer) drug. It’s just one of many drugs researchers have attempted to repurpose as an anti-aging elixir. The latest discovery comes from scientists in China who have found that liraglutide, a drug similar to Ozempic, improves bone health in diabetic rats. Moreover, the bone anti-aging effects of liraglutide were mediated by sirtuin 1 (SIRT1), an important enzyme everyone should know about. 

Anti-Aging Sirtuin Activators 

Sirtuins (SIRTs) are a family of seven enzymes that regulate critical signaling pathways involved in numerous biological processes. SIRTs use NAD+ as fuel, one reason why elevating cellular NAD+ levels with NAD+ precursors like NMN (nicotinamide mononucleotide) counteracts biological aging. Extensive studies have demonstrated that SIRTs regulate aging through processes such as senescence, metabolic regulation, DNA stability, and circadian rhythms. 

SIRT activators are highly sought-after molecules for their potential to protect multiple organ systems from chronic diseases, including cancer, kidney disease, Alzheimer’s disease, fatty liver disease, lung disease, and heart disease. SIRT activation could potentially explain how Ozempic reduces death rates and lowers the risk of death from cardiovascular causes. For example, SIRTs are implicated in their protective role against many cardiovascular-related conditions. 

(Wu et al., 2022) Protective Roles of Sirtuins on the Circulatory System. Sirtuins play a protective role in many age-related conditions.

Sirtuin Activation Necessary for Liraglutides Anti-Aging Effects 

While they have become known for their weight-loss effects, GLP-1 receptor agonists are mainly prescribed to combat type 2 diabetes, a chronic metabolic disorder characterized by high blood glucose levels. High blood glucose levels wreak havoc on nearly every organ system, including bone, where it accelerates bone loss and increases the risk of fractures.

To explore the effects of GLP-1 receptor agonists on diabetes, Chinese scientists injected diabetic rats with 0.2 mg/kg of liraglutide for 12 weeks. This resulted in weight loss and lower blood glucose levels, indicating that liraglutide has similar effects in rats as it does in humans. The liraglutide also improved bone metabolism as shown by increased bone formation and decreased bone breakdown markers. Importantly, the liraglutide treatment increased SIRT1 levels in the bone tissue of the diabetic rats. 

To confirm the critical role of SIRT1, the researchers genetically removed SIRT1 from the diabetic rats. Where liraglutide reduced inflammation and oxidative stress, which are established biological drivers of aging, in diabetic rats with SIRT1 intact, removing SIRT1 blocked this effect. Moreover, removing SIRT1 blocked the bone formation effects of liraglutide, demonstrating that the bone anti-aging effects of this GLP-1 agonist are mediated by SIRT1. 

(Zhong et al., 2024) Liraglutide Reduces Inflammation via SIRT1. Compared to normal rats, diabetic rats (red) exhibit higher levels of inflammation (Serum IL-6). Treating diabetic rats with liraglutide (green and orange), reduces inflammation unless SIRT1 is blocked (blue).

Combining Sirtuin Activators with NAD+ Precursors 

Harvard professor and leading aging biology researcher David Sinclair, PhD, recently took to X to discuss whether NAD+ boosters like NMN can work with GLP-1 drugs. He cites studies showing that NMN improves bone mass in mice, liraglutide improves bone formation in women, NMN improves fracture healing in mice, and SIRT1’s potential role in bone metabolism. Sinclair then points out that GLP-1 drugs have side effects like muscle mass loss that can potentially be mitigated by NAD+ precursors like NMN. He cites a study showing that NMN improves leg endurance in adults, suggesting NMN could protect against muscle loss. 

Nevertheless, whether combining NMN or other NAD+ precursors with GLP-1 receptor agonists like Ozempic provides additive effects will require further research. To our knowledge, there are no studies that have tested the combined effects of these compounds. However, combining NAD+ boosters with sirtuin activators has already been tested in humans. A clinical trial showed that the NAD+ precursor NR (nicotinamide riboside) combined with the sirtuin activator pterostilbene reduced liver inflammation in adults. This means that combining NAD+ boosting technologies with sirtuin activation technologies may provide additive or syngenetic effects. Some products that combine NAD+ with sirtuin activation, such as Restorin, are already on the market.