New study aims to elucidate the role of p21 in chronic lung inflammation

A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 7, entitled, "p21 facilitates chronic lung inflammation via epithelial and endothelial cells."

Cellular senescence is a stable state of cell cycle arrest that regulates tissue integrity and protects the organism from tumorigenesis. However, the accumulation of senescent cells during aging contributes to age-related pathologies. One such pathology is chronic lung inflammation.

p21 (CDKN1A) regulates cellular senescence via inhibition of cyclin-dependent kinases (CDKs). However, its role in chronic lung inflammation and functional impact on chronic lung disease, where senescent cells accumulate, is less understood. In this new study, researchers Naama Levi, Nurit Papismadov, Julia Majewska, Lior Roitman, Noa Wigoda, Raya Eilam, Michael Tsoory, Ron Rotkopf, Yossi Ovadya, Hagay Akiva, Ofer Regev, and Valery Krizhanovsky from the Weizmann Institute of Science aimed to elucidate the role of p21 in chronic lung inflammation.

"[...] we subjected p21 knockout (p21-/-) mice to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to chronic bronchitis and accumulation of senescent cells."

The researchers utilized a lipopolysaccharide (LPS) inhalation-induced chronic bronchitis procedure to study the effects of repetitive LPS exposure on p21 knockout (p21-/-) mice. Furthermore, the team aimed to examine the specific contribution of the epithelial, endothelial and immune compartments to chronic bronchitis pathology. They found that p21 knockout led to a reduced presence of senescent cells, alleviated the pathological manifestations of chronic lung inflammation, and improved the fitness of the mice. The expression profiling of the lung cells revealed that resident epithelial and endothelial cells, but not immune cells, play a significant role in mediating the p21-dependent inflammatory response following chronic LPS exposure.

"Therefore, we suggest that p21-dependent elimination of senescent cells may limit the damage induced by the pro-inflammatory presence of senescent cells, but also promote tissue regeneration. Therefore, inhibition of p21 represents a promising strategy for limiting age-related inflammatory disorders in general and obstructive lung diseases in particular."