Study of the impact of the DDR pathway in UVB-induced senescent keratinocytes

Abstract

The aging of the population is a global phenomenon accompanied by an increase in age-related diseases. Skin aging is particularly intriguing as it depends on intrinsic and extrinsic factors. Throughout life, the skin is an organ especially exposed to external stressors such as ultraviolet rays (UV). UVB radiation, a subset of UV rays, emerges as a significant contributor to skin aging. The latter can cause DNA damage, oxidative stress, inflammation, and induce senescence in normal human epidermal keratinocytes (NHEKs). Senescent keratinocytes exhibits distinct characteristics including cell cycle arrest, increased beta-galactosidase activity (SA-βgal), persistent DNA damage, and a secretome commonly referred to as the senescence-associated secretory phenotype (SASP). However, it is not yet known how senescent cells appear in vivo. Persistent DNA damage induced by repeated UVB exposure in NHEKs activate the DNA damage response (DDR) pathway. The objective of this Master's thesis is to determine whether the DDR pathway is involved in the establishment of the senescent phenotype following UVB exposures. We will assess DDR activation after the last UVB stress and investigate the impact of its inhibition on the development of UVB-induced senescence.

Date of Award	15 Jan 2024
Original language	English
Awarding Institution	University of Namur
Supervisor	Florence Debacq-Chainiaux (Supervisor)