A twin study published in GeroScience has yielded results suggesting that calcium channel blockers, drugs that are commonly used to treat hypertension and other diseases, slow down epigenetic aging and may lengthen healthy lifespan.
A wide field
The researchers begin this paper by noting that over 400 compounds, as found in the DrugAge database, have been reported to extend lifespan in model organisms [1]. However, getting human data for the efficacy of these drugs against any of the processes of aging is considerably more difficult. Therefore, researchers normally try use surrogate endpoints that correspond to lifespan (biomarkers) [2].
Some drugs, however, already appear to be associated with lifespan. The researchers placed their focus on antihypertensive, antidiabetic, and lipid-lowering drugs, which are widely consumed by a substantial fraction of the US population [3], have been reported to have beneficial effects against other age-related diseases: statins are linked to a reduced incidence of dementia [4] and metformin is linked to a decrease in cancer incidence [5].
Previous studies have attempted to examine the relationship between these sorts of drugs and DNA methylation clocks [6]. However, while these clocks are valuable, they are not always comprehensively robust, and so these researchers aimed to use considerably more biomarkers.
A robust twin study with multiple layers of information
This paper uses data from SATSA, a Swedish twin study that focuses on twins that were raised together or apart. Participants who were at least 50 years old received in-person examinations for 3 years between 1986 and 2014, creating a wide body of evidence. After exclusions for contradictory or incomplete information, 672 people with 2,746 measurements were included in the results analyzed here.
There were a total of 12 different biomarkers, including measurements of DNA methylation (including DunedinPACE and GrimAge), telomere length, physical frailty, functional age, and cognitive decline. Many of these biomarkers were composites of related biomarkers. The medications taken by the participants were self-reported, which was corroborated by purchase data.
Advanced statistical analysis was performed on these results, controlling for confounding variables and correlating multiple drugs. As this was a long-term study, it was possible to conduct individual analyses, comparing people’s measurements before and after they were consuming certain medications. The researchers’ model also took into account the diseases that had caused the participants to be taking such medications in the first place.
A confluence of factors
Unsurprisingly, the people who did and didn’t take medications of all types had significant demographic differences. Medication takers were older and had higher BMIs and blood pressure.
Depending on how the researchers analyzed their measurements at the individual level, certain patterns began to emerge. The number of participants who took antidiabetic drugs was too low to draw any significant conclusions. However, in a model that controlled for individual biases, antihypertensive drugs were found to be associated with a lower GrimAge.
While some antihypertensive drugs were individually found to be associated with better cognition but negative effects on epigenetic aging, calcium channel blockers were associated with multiple functional biomarkers along with decreased methylation aging according to multiple epigenetic clocks.
Conclusion
This study is interesting for both its positive and negative results. With statistical results such as these, the biological effects of calcium channel blockers on human beings warrant further investigation. On the other hand, these results make it clear that while they are effective against the specific disorders that they are prescribed for, the vast majority of drugs do not appear to have any noticeable effects on biological aging.
Literature
[1] Barardo, D., Thornton, D., Thoppil, H., Walsh, M., Sharifi, S., Ferreira, S., … & de Magalhães, J. P. (2017). The DrugAge database of aging‐related drugs. Aging cell, 16(3), 594-597.
[2] Lohman, T., Bains, G., Berk, L., & Lohman, E. (2021). Predictors of biological age: The implications for wellness and aging research. Gerontology and Geriatric Medicine, 7, 23337214211046419.
[3] Hales, C. M., Servais, J., Martin, C. B., & Kohen, D. (2019). Prescription drug use among adults aged 40–79 in the United States and Canada.
[4] Jick, H. Z. G. L., Zornberg, G. L., Jick, S. S., Seshadri, S., & Drachman, D. A. (2000). Statins and the risk of dementia. The Lancet, 356(9242), 1627-1631.
[5] Gandini, S., Puntoni, M., Heckman-Stoddard, B. M., Dunn, B. K., Ford, L., DeCensi, A., & Szabo, E. (2014). Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and ConfoundersMetformin Meta-Analysis. Cancer prevention research, 7(9), 867-885.
[6] Gao, X., Colicino, E., Shen, J., Just, A. C., Nwanaji-Enwerem, J. C., Coull, B., … & Baccarelli, A. A. (2018). Accelerated DNA methylation age and the use of antihypertensive medication among older adults. Aging (Albany NY), 10(11), 3210.
