Senolytics: Antibiotics Identified As Potential Anti-aging Drugs

An FDA-approved antibiotic – Azithromycin – can effectively target and eliminate senescent cells in culture, according to the results of new research carried out in the UK. The research team, from the University of Salford’s Translational Medicine Laboratories, compared the effects of a panel of FDA-approved drugs, on i) normal cells and ii) senescent cells, derived from human skin and lungs.

Genetic experiments that eliminate “senescent” cells – older cells, which lose the ability to divide – have already been proven to alleviate age-related dysfunction in model organisms.

At a single low-dosage, Azithromycin was shown to effectively kill and eliminate the senescent cells, with an efficiency of 97 percent. Moreover, the normal healthy cells thrived in the presence of Azithromycin.

Senescent Cells

Senescence is a clear hallmark of normal chronological aging. Senescent cells are thought to be the “root cause” for many ageing-associated diseases, such as cancer, heart disease, diabetes and dementia, among others.

“It was an astonishing result, and one that got us thinking about the implications for treating or preventing a variety of ageing-associated diseases. Azithromycin is a relatively mild antibiotic that has been proven to extend lifespan in cystic fibrosis patients by several years. Originally, the thinking was that Azithromycin is killing harmful bacteria in cystic fibrosis patients – but our tests now shed a new light on what might be actually going on.

Our new interpretation is that the antibiotic is probably eliminating the “inflammatory” fibroblasts, in other words, the senescent cells that are normally associated with ageing. If that is the case, then we may have unearthed a very inexpensive and readily available method of eliminating ageing cells that are toxic to the body,”

said Professor Michael P. Lisanti, the research lead.

Senolytic Antibiotics

The Salford team members say that the antibiotic selectively targets senescent ageing cells, by altering their metabolic properties, forcing them to undergo cell death. Such a drug is said to be “senolytic,” as it lyses or destroys senescent cells.

Chemical structures of Erythromycin and related compounds

Chemical structures of Erythromycin and related compounds
Credit: Bela Ozsvari et al. CC-BY

The team also found a second related antibiotic, Roxithromycin, which also depletes senescent cells in a similar way, but with less selectivity.

“If we consider our results and then we also consider what results have been achieved in clinical trials with cystic fibrosis patients, we are probably looking at the same mechanism(s), whereby antibiotics are removing inflammatory senescent cells and boosting healthy ones. Undoubtedly, our results have significant implications for potentially alleviating or reversing tissue dysfunction and slowing the development of many ageing-associated diseases,”

explains Professor Federica Sotgia, a co-lead of this study.

The work was supported by research grant funding, provided by Lunella Biotech, Inc.

Ozsvari B, Nuttall JR, Sotgia F, Lisanti MP
Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts
Aging (Albany NY). 2018 Nov 14. https://doi.org/10.18632/aging.101633