We typically think of prescription drugs as targeted treatments designed to address the underlying mechanisms and biochemical pathways associated with specific diseases or conditions. For example, healthcare providers commonly prescribe statins that lower cholesterol levels and reduce cardiovascular disease risk by inhibiting the enzyme involved in cholesterol synthesis. Similarly, doctors might prescribe antibiotics to target bacterial infections by disrupting the bacteria's growth or killing them outright.

But prescription drugs may have multiple uses or indications beyond their original intended purpose. A recent preprint from the biotech startup EPITERNA describes a study exploring the link between prescription drugs and human lifespan. Researchers analyzed more than 40 years of prescription drug data from over 500,000 patients in the UK Biobank to examine how commonly prescribed medications affect mortality risk. Many drugs have negative consequences for lifespan for reasons that include drug resistance, drug dependency, and side effects such as organ damage and immunosuppression—but a number of drugs actually appear to be beneficial for longevity. In this episode, Matt goes over the study's top-performing drugs for lifespan, and discusses how we might interpret and extend these intriguing findings about common prescription medications.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Association between prescription drugs and all-cause mortality risk in the UK population

This is the EPITERNA preprint Matt discusses in the podcast. The preprint describes the results of analyzing prescription medication and mortality data from over half a million patients recorded in the UK Biobank, a biomedical database and research resource of health-related data from participants aged between 40 and 69 years old in the United Kingdom, for a period of over 40 years. After comparing the mortality of patients taking the top 406 prescribed drugs to that of controls not taking a given drug, they found a number of prescription medications correlated with longer lifespans.

Effect of Aspirin on All-Cause Mortality in the Healthy Elderly

Aspirin, also known as acetylsalicylic acid, is one of the most widely used medications globally, renowned for its pain-relieving, anti-inflammatory, and blood-thinning properties. Its accessibility, affordability, and proven efficacy in pain relief contribute to its frequent use. This study found that healthy older adults taking daily aspirin had a higher risk of death than those taking placebo drugs, and that most deaths were cancer-related.

Geroscience-guided repurposing of FDA-approved drugs to target aging: A proposed process and prioritization

This article makes the case for a greater focus on repurposing existing drugs to target the biology of aging and age-related disease. The authors, who trawled the literature for FDA-approved drugs or drug classes that have a potential lifespan-extending effect in rodents, present a framework for assessing whether a given therapeutic might demonstrate geroprotective effects in a clinical trial.

The Mortality Toll of Estrogen Avoidance: An Analysis of Excess Deaths Among Hysterectomized Women Aged 50 to 59 Years

In the preprint Matt discusses in this podcast episode, six prescription medications containing estrogen had a positive impact on mortality risk. That is a striking result, and one worth further exploration. This paper examined the mortality toll of estrogen avoidance among middle-aged women who had undergone hysterectomies, and found that nearly 20,000 hysterectomized women had experienced premature death after the publication of findings that led to an aversion to hormone replacement therapy.

Canagliflozin extends life span in genetically heterogeneous male but not female mice

Matt mentions this study in the podcast as one showing that canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor aimed at treating type 2 diabetes, was one of the more potent mouse lifespan-extending drugs to emerge from the Interventions Testing Program. Canagliflozin extended male mouse lifespan by 14 percent, and the age for 90th percentile survival by nine percent. The study found no lifespan extension effects in female mice.