The global population is aging rapidly—life expectancy has almost doubled in the last 150 years and in 2024 is 73.3 years. According to the 2023 World Social Report from the United Nations1, the percentage of people aged 65 and older has increased from 5% in 1970 to 10% in 2020 and it is expected to be above 15% by 2050 (Fig. 1). However, despite gains in life expectancy, the proportion of healthy years remains largely unchanged, with additional lifespan often burdened by chronic diseases and progressive decline in physical and mental functions2. Extended longevity inevitably leads to multiple age-related diseases, requiring long-term use of numerous medications to manage these conditions3.

Fig. 1
Fig. 1
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Distribution of the world population demographics reproduced from the United Nations World Social Report 20231 (left; black line marks the present date) and drug safety demographics from the United States Food and Drug Administration Adverse Event Reporting System (right) across broad age groups.

Every single medication is associated with adverse reactions4. This risk becomes significantly greater in the context of polypharmacy, where the concurrent use of multiple drugs leads to cumulative side effects and a greater potential for harmful drug interactions3. This is a major concern for an aging population as older patients are not only more likely to be treated with polypharmacy regimens but also more susceptible to their associated risks compared to younger populations. Indeed, aging is associated with changes in organ function, such as liver shrinkage and reduced kidney filtration, which alter drug metabolism and elimination. These alterations ultimately increase the frequency and seriousness of adverse drug reactions, potentially becoming a limiting factor for healthy aging5.

Currently, the primary source for identifying drug-related safety events is randomized clinical trials. Unfortunately, older adults are often excluded from clinical trials as multimorbidity, polypharmacy, and age-related conditions can obscure the detection of adverse reactions causally linked to drug action6. Although measures such as the STOPP/START and Beers criteria exist to modify drug dosages and mitigate safety risks in the older populations7, the true impact of adverse drug reactions in older patients is not detected until drugs reach the market.

Post-marketing databases collect a large volume of individual case safety reports (ICSR) of drugs, spontaneously deposited by both health professionals and patients worldwide. Despite their inherent limitations8, ICSR repositories are routinely used to detect safety signals of disproportionate reporting among patient subpopulations poorly represented in clinical trials9. The United States Food and Drug Administration Adverse Event Reporting System (FAERS) contains a total of 23,880,384 ICSRs, of which approximately 61% contain patient age annotations. Interestingly, following global demographic trends, the proportion of patients aged 65 and older in FAERS has grown steadily, increasing from 20% in 1970 to 40% in 2020 (Fig. 1). At this pace, ICSR databases will soon be mainly populated by drug safety reports from older adults, which will make them even more invaluable to monitor the emergence of safety signals that affect the quality of life of this vulnerable and growing subpopulation9.

Healthy aging aims at reducing the healthspan-lifespan gap in an increasingly aging population. Unfortunately, far from improving, the gap continues to widen2. The ongoing challenge to match longer lifespans with improved health raises important questions about the role of healthcare systems in supporting older adults. Intriguingly, a recent study in Colombia found that a substantial portion of its centenarians, regarded as the ultimate model of healthy aging, often reside in remote rural areas with limited access to healthcare10. This highlights an urgent need for coordinated action to assess how drug safety is, and will increasingly become, a limiting factor in healthy aging. With geroprotective strategies still in their infancy and no interventions yet able to effectively prevent or delay age-related diseases11, developing a deeper understanding of drug safety in an aging population, along with closer monitoring and managing, is essential to realize the aspiration of a future of healthy longevity.