BUFFALO, NY- December 20, 2023 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 23, entitled, “Benidipine calcium channel blocker promotes the death of cigarette smoke-induced senescent cells and improves lung emphysema.”

Smoking is the main risk factor for many lung diseases including chronic obstructive pulmonary disease. Cigarette smoke (CS) contains carcinogenic and reactive oxygen species that favor DNA mutations and perturb the homeostasis and environment of cells. CS induces lung cell senescence resulting in a stable proliferation arrest and a senescence-associated secretory phenotype. It was recently reported that senescent cell accumulation promotes several lung diseases.

In this new study, researchers Alberta Palazzo, Gabriela Makulyte, Delphine Goerhig, Jean-Jacques Médard, Vincent Gros, François Trottein, Serge Adnot, David Vindrieux, Jean-Michel Flaman, and David Bernard from Université de Lyon, Equipe Labellisée la Ligue Contre le Cancer, Université Paris Est Créteil, Hôpital Henri Mondor, and Université Lille performed a chemical screen, using an FDA-approved drug library, to identify compounds selectively promoting the death of CS-induced senescent lung cells.

“Here, our aim was to identify senolytic compounds in the context of CS-induced senescence and to assess whether they improved lung emphysema.”

Aside from the well-known senolytic, ABT-263, the researchers identified other potentially new senescence-eliminating compounds, including a new class of molecules, the dihydropyridine family of calcium voltage-gated channel (CaV) blockers. Among these blockers, Benidipine decreased senescent lung cells and ameliorates lung emphysema in a mouse model. The dihydropyridine family of CaV blockers thus constitutes a new class of senolytics that could improve lung diseases.

“Hence, our work paves the way for further studies on the senolytic activity of CaV blockers in different senescence contexts and age-related diseases.”

DOI - https://doi.org/10.18632/aging.205259

Corresponding author - David Bernard - [email protected]

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Keywords - aging, senolytic, cigarette smoke, lung disease, cellular senescence, calcium channel

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Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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