Could senolytic therapies designed to remove senescent cells, which accumulate with age, potentially be used to treat asthma? The researchers of a recent review certainly believe this could be the case, and there is plenty of reason to think they could be right.
Senescent cells and aging
As we grow older, increasing amounts of our cells enter into a state known as senescence. Senescent cells no longer divide to create new healthy cells, and they stop supporting the tissues and organs of which they are part.
If that was not bad enough, senescent cells also secrete a range of harmful pro-inflammatory chemical signals (cytokines) that can cause nearby cells to become senescent too; these secreted signals are collectively known as the senescence-associated secretory phenotype (SASP). A relatively small number of senescent cells can cause widespread problems if left to linger in the body.
Their presence causes many problems: they degrade tissue function, increase levels of chronic inflammation, and can even eventually raise the risk of cancer. Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of these senescent cells escape this process and build up.
By the time people reach old age, significant numbers of these senescent cells have accumulated in the body, causing inflammation and damage to surrounding cells and tissues. The accumulation of senescent cells is a proposed cause of aging and plays a key role in the onset and progression of age-related diseases as well as other conditions.
One proposed solution to the problem is the removal of these harmful senescent cells with drugs capable of causing them to self-destruct; such drugs are known as senolytics.
Senolytics and asthma
Today, we want to highlight a recent review that looks at the role of senescent cells in the context of asthma [1]. Its researchers discuss how senescent cells play a role in the development of age-related diseases such as chronic obstructive pulmonary diseases (COPD) and idiopathic pulmonary fibrosis (IPF). They then go on to explore the association between asthma and senescent cells.
The review also discusses potentially using senolytics for the treatment of asthma and touches upon azithromycin as a potential candidate. Azithromycin is an antibiotic originating from erythromycin, and it has bactericidal properties, appears to be anti-inflammatory, and is capable of regulating inflammatory responses [2]. The researchers discuss the potential of this particular antibiotic including the fact that in 2018, azithromycin showed its potential as a senolytic drug by removing around 97% of senescent human lung fibroblasts during an in vitro study [3]. This could mean that azithromycin is a senolytic with the potential to reduce the SASP in asthmatic lungs. The review also touches upon other senolytic drugs and compounds and is well worth reading.
Cellular senescence is a complicated process featured by irreversible cell cycle arrest and senescence-associated secretory phenotype (SASP), resulting in accumulation of senescent cells, and low-grade inflammation. Cellular senescence not only occurs during the natural aging of normal cells, but also can be accelerated by various pathological factors. Cumulative studies have shown the role of cellular senescence in the pathogenesis of chronic lung diseases including chronic obstructive pulmonary diseases (COPD) and idiopathic pulmonary fibrosis (IPF) by promoting airway inflammation and airway remodeling. Recently, great interest has been raised in the involvement of cellular senescence in asthma. Limited but valuable data has indicated accelerating cellular senescence in asthma. This review will compile current findings regarding the underlying relationship between cellular senescence and asthma, mainly through discussing the potential mechanisms of cellular senescence in asthma, the impact of senescent cells on the pathobiology of asthma, and the efficiency and feasibility of using anti-aging therapies in asthmatic patients.
Conclusion
It is highly likely that senescent cells play a significant role in the development and progression of asthma as they do in many other conditions, both age-related and otherwise. These researchers have done a great job at compiling some interesting information and in exploring the potential of senolytics to treat yet another disease.
Today, there are many companies developing senolytic drugs, and it is highly likely that this particular approach will be the first available repair-based therapy that directly targets one of the aging processes in order to prevent, delay, or even reverse age-related diseases.
Literature
[1] Wang, Z. N., Su, R. N., Yang, B. Y., Yang, K. X., Yang, L. F., Yan, Y., & Chen, Z. G. (2020). Potential Role of Cellular Senescence in Asthma. Frontiers in Cell and Developmental Biology, 8, 59.
[2] Kanoh, S., & Rubin, B. K. (2010). Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clinical microbiology reviews, 23(3), 590-615.
[3] Ozsvari, B., Nuttall, J. R., Sotgia, F., & Lisanti, M. P. (2018). Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts. Aging (Albany NY), 10(11), 3294.
