Key anti-aging drugs for mice
Research has identified several compounds that can extend the lifespan and healthspan of mice by modulating fundamental aging pathways. Many of these drugs were evaluated by the National Institute on Aging's (NIA) Interventions Testing Program (ITP), a gold standard for longevity studies in mice.
Rapamycin
Rapamycin, also known as sirolimus, is a well-established anti-aging drug in mice and is typically used to prevent organ rejection in transplant patients. It works by inhibiting the mechanistic target of rapamycin (mTOR) signaling pathway, which plays a central role in regulating cell growth, metabolism, and aging. Long-term administration has been shown to increase the mean lifespan of mice by 10–18%, depending on the study. A short course of rapamycin treatment has also demonstrated anti-aging benefits in mice.
Acarbose
Acarbose is an alpha-glucosidase inhibitor commonly used to treat type 2 diabetes by slowing down the digestion of complex carbohydrates. In mice studies conducted by the ITP, acarbose treatment significantly extended the lifespan, particularly in males, who saw a median lifespan increase of about 20%. The effect was less pronounced in female mice. Its anti-aging mechanism is thought to be related to its effects on glucose and insulin signaling, mimicking some of the benefits of caloric restriction.
Senolytics
Senolytics are a class of drugs that work by selectively eliminating senescent cells—old, damaged cells that accumulate with age and contribute to inflammation and tissue dysfunction. A senolytic cocktail of dasatinib plus quercetin has been shown to alleviate age-related symptoms in mice and extend their lifespan. By clearing these harmful cells, senolytics can promote tissue rejuvenation and delay the onset of age-related diseases.
NAD+ boosters
Compounds that boost levels of nicotinamide adenine dinucleotide (NAD+), such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), have shown promise in mouse studies. NAD+ levels decline with age, and replenishing them can improve various age-related conditions in mice, including metabolic function, physical activity, and mitochondrial health. While some NAD+ precursors have extended lifespan in specific mouse models, results have been mixed in normal aging mice.
Combination therapies in mice
Researchers are increasingly exploring drug cocktails to target multiple aging pathways simultaneously, which has yielded more robust results than single-drug treatments.
Comparison of Single vs. Combination Therapy in Mouse Longevity
| Drug Treatment | Target Pathway | Individual Effect on Lifespan | Combination Effect |
|---|---|---|---|
| Rapamycin | mTOR signaling | 15–20% increase | ~30% increase with trametinib |
| Trametinib | Ras/MEK/ERK signaling | 5–10% increase | ~30% increase with rapamycin |
| Acarbose | Nutrient signaling | Up to 22% (male-specific) | More effective in cocktail with rapamycin and phenylbutyrate |
| Senolytics (e.g., D+Q) | Senescent cells | Significant life extension | Often administered as a cocktail for optimal efficacy |
Other promising anti-aging compounds
Other drugs and compounds have demonstrated anti-aging effects in mice:
- 17-α-estradiol: A variant of estrogen that has shown lifespan-extending effects specifically in male mice.
- Canagliflozin: A diabetes drug that has also been found to increase lifespan in male mice.
- Spermidine: This natural polyamine, which declines with age, extends mouse lifespan by activating autophagy, the body's cellular cleanup process.
- Resveratrol: While less consistently effective than other compounds in normal-diet mice, this sirtuin activator has extended healthspan and lifespan in mice on a high-fat diet.
- Astaxanthin and Meclizine: The NIA ITP has shown that these compounds can also extend the lifespan of mice.
Conclusion
Significant progress has been made in identifying what are anti-aging drugs for mice, with compounds like rapamycin, acarbose, and senolytics demonstrating the ability to extend both lifespan and healthspan. These preclinical studies provide a foundation for understanding the mechanisms of aging and testing potential therapeutic strategies. While these drugs are not currently approved for anti-aging use in humans, the research in mice provides a roadmap for future clinical investigations and the eventual development of human geroprotective treatments. Ongoing research continues to refine dosing, identify optimal combinations, and uncover new pathways, moving science closer to addressing age-related decline.
