Longevity: Exploring the Science of a Longer, Healthier Life

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Written By Adama Diarra, DO, FACP

Chapter 8: Exploring Clinically Proven Medications for Human Longevity

As of now, no prescription medications in the U.S. have been proven in large-scale, randomized controlled trials to extend human lifespan and are FDA-approved specifically for longevity or anti-aging purposes.

However, a few FDA-approved medications, primarily for other conditions, have shown evidence-based associations with increased lifespan or reduced mortality in specific populations. Importantly, these are not approved for general anti-aging use, but their effects on healthspan (the healthy years lived) or even lifespan have been observed in certain cohorts

In the quest for extending human lifespan and promoting healthy aging, several medications have emerged with potential benefits. Below is an overview of some clinically studied drugs, detailing their mechanisms, costs, advantages, and potential drawbacks.​


1. Metformin

  • Mechanism of Action: Metformin primarily reduces hepatic glucose production and enhances insulin sensitivity. It activates AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis, which may influence aging processes.​  It may also affect the mammalian Target of Rapamycin (mTOR) pathway which is a complex cellular signaling network that plays a crucial role in regulating various physiological processes, including cell growth, metabolism, autophagy (process that recycles cellular components for energy production) and immune function. Evidence from a landmark trial TAME (Targeting Aging with Metformin) supports metformin at least delays age-related diseases. When this was release, I first noticed some of my physician patients ask me for a metformin prescription. Then, as awareness increased, more and more people starting asking . 

  • Cost: Generic metformin is relatively affordable, with monthly costs ranging from $4 to $20, depending on dosage and location.​

  • Pros:

    • Extensive safety profile established over decades.​

    • Potential benefits beyond glucose control, including cardiovascular protection and possible anticancer properties (Janin, 2025)

  • Cons:

    • Common side effects include gastrointestinal disturbances such as nausea and diarrhea.​

    • Rare risk of lactic acidosis, particularly in individuals with renal impairment.​

    • While observational studies suggest reduced mortality in diabetic patients, conclusive evidence for lifespan extension in non-diabetic individuals is lacking.


2. Rapamycin

  • Mechanism of Action: Rapamycin inhibits the mechanistic target of rapamycin (mTOR), a protein that regulates cell growth and metabolism. By suppressing mTOR activity, rapamycin may mimic caloric restriction's effects, promoting autophagy and potentially delaying aging (Mannick et al, 2014)

  • Cost: Rapamycin's cost varies widely based on formulation and region, with estimates ranging from $100 to over $1,000 monthly.​

  • Pros:

    • In animal models, rapamycin has extended lifespan and delayed age-related diseases (Attia & Gifford, 2023). ​

    • Potential neuroprotective effects and reduced cancer incidence observed in preclinical studies. ​

  • Cons:

    • Immunosuppressive properties may increase infection risk.​

    • Side effects can include mouth ulcers, hyperlipidemia, and impaired wound healing.​

    • Long-term safety and efficacy in healthy humans remain uncertain, necessitating further research. ​


3. GLP-1 Receptor Agonists (e.g., Semaglutide)

  • Mechanism of Action: Glucagon-like peptide-1 (GLP-1) receptor agonists enhance insulin secretion, suppress glucagon release, and slow gastric emptying, leading to improved glycemic control and weight loss (Collins & Costello, 2024)

  • Cost: These medications can be expensive, with monthly costs often exceeding $800 without insurance coverage.​

  • Pros:

    • Effective in managing type 2 diabetes and promoting significant weight loss. ​

    • Emerging evidence suggests potential benefits in reducing risks of cardiovascular diseases and possibly Alzheimer's disease. ​

  • Cons:

    • Common side effects include nausea, vomiting, and diarrhea.​

    • Potential for rare but serious adverse events like pancreatitis. ​

    • High cost may limit accessibility for some individuals.​

4. Senolytics (e.g., Dasatinib and Quercetin)

  • Mechanism of Action: Senolytics are agents that selectively induce death of senescent cells, which accumulate with age and contribute to chronic inflammation and tissue dysfunction (Khalil et al, 2023)

  • Cost: Varies widely; dasatinib is a prescription cancer drug and can be costly, while quercetin is an over-the-counter supplement and relatively inexpensive.​

  • Pros:

    • Animal studies have shown improved physical function and extended lifespan. ​

    • Potential to alleviate age-related diseases by reducing senescent cell burden. ​

  • Cons:

    • Human studies are limited, with ongoing research needed to establish safety and efficacy. ​

    • Potential side effects and optimal dosing regimens are not well-defined.​

    • Use outside clinical trials is not currently recommended due to insufficient evidence.​

Conclusion

While these medications show promise in promoting longevity, it's essential to approach them with caution. Most have been approved for specific medical conditions, and their use as anti-aging therapies is not yet well-established. Potential benefits must be weighed against risks, costs, and the current lack of robust human data supporting their efficacy in extending lifespan. Individuals should consult healthcare professionals before considering such treatments and rely on evidence-based lifestyle interventions—such as a balanced diet, regular exercise, and adequate sleep—to support healthy aging.


References

  • Attia, P., & Gifford, B. (2023). Outlive: The science and art of longevity. Harmony Books.Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a tool to target aging. Cell Metabolism, 23(6), 1060-1065.​

  • Baker, D. J., & Petersen, R. C. (2018). Cellular senescence in brain aging and neurodegenerative diseases: Evidence and perspectives. *Journal of Clinical Investigation, 128*(4), 1208–1216. https://doi.org/10.1172/JCI95148

  • Collins, L., & Costello, R. A. (2024). Glucagon-like peptide-1 receptor agonists. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK551568/Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013). mTOR is a key modulator of ageing and age-related disease. Nature, 493(7432), 338-345.​

  • Khalil, R., Diab-Assaf, M., & Lemaitre, J.-M. (2023). Emerging therapeutic approaches to target the dark side of senescent cells: New hopes to treat aging as a disease and to delay age-related pathologies. Cells, 12(6), 915. https://doi.org/10.3390/cells12060915

  • Janin, A. (2025, March 10). Ozempic’s new frontier: The war on aging. The Wall Street Journal. https://www.wsj.com/health/wellness/ozempic-weight-loss-drug-aging-health-benefits-d93a22f8

  • Justice, J. N., Nambiar, A. M., Tchkonia, T., Lebrasseur, N. K., Pascual, R., Hashmi, S. K., ... & Kirkland, J. L. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. *EBioMedicine, 40*, 554–563. https://doi.org/10.1016/j.ebiom.2018.12.052

  • Kulkarni, A. S., Gubbi, S., & Barzilai, N. (2020). Benefits of metformin in attenuating the hallmarks of aging. *Cell Metabolism, 32*(1), 15–30. https://doi.org/10.1016/j.cmet.2020.04.001

  • Mannick, J. B., Del Giudice, G., Lattanzi, M., Valiante, N. M., Praestgaard, J., Huang, B., ... & Kunkel, E. J. (2014). mTOR inhibition improves immune function in the elderly. Science Translational Medicine, 6(268), 268ra179. https://doi.org/10.1126/scitranslmed.3009892 

  • Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., ... & Nauck, M. A. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. *New England Journal of Medicine, 375*(19), 1834–1844. https://doi.org/10.1056/NEJMoa1607141

  • Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F., Nauck, M. A., ... & LEADER Steering Committee. (2016). Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, 375(4), 311–322. https://doi.org/10.1056/NEJMoa1603827