BibTex format
@article{Devulder:2026:10.1111/acel.70487,
author = {Devulder, JV and Fenwick, PS and Kolosionek, E and AlSahaf, M and Viola, P and Lemaire, R and Razdan, N and Kudo, H and Sinadinos, A and Odqvist, L and Donnelly, LE and Barnes, PJ},
doi = {10.1111/acel.70487},
journal = {Aging Cell},
title = {Clearance of Senescent Cells by <scp> BCL <sub>XL</sub> </scp> <scp>PROTAC</scp> : A Novel Approach to Treat <scp>COPD</scp> ?},
url = {http://dx.doi.org/10.1111/acel.70487},
volume = {25},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - <jats:title>ABSTRACT</jats:title> <jats:p> Ageing and cellular senescence significantly contribute to the progression of agerelated diseases, particularly chronic obstructive pulmonary disease (COPD). Cellular senescence refers to the cessation of cell division in response to stress and damage. While senescent cells remain metabolically active, they secrete proinflammatory factors that drive disease progression. Senolytic therapies aim to selectively target and eliminate these senescent cells by inducing their apoptosis. This study examines the senolytic potential of BCL <jats:sub>XL</jats:sub> PROTAC, a novel proteolysistargeting chimera designed to degrade BCL <jats:sub>XL</jats:sub> , in small airway epithelial cells and fibroblasts from patients with COPD. Treatment of COPD small airway epithelial cells and fibroblasts with BCL <jats:sub>XL</jats:sub> PROTAC led to their apoptosis through the activation of caspase 3, along with a reduction in senescence markers such as p21 <jats:sup>CIP1</jats:sup> , p16 <jats:sup>INK4a</jats:sup> and senescenceassociated βgalactosidase. The effects of BCL <jats:sub>XL</jats:sub> PROTAC were selective for senescent cells and did not affect nonCOPD cells. The clearance of COPD small airway epithelial cells and fibroblasts by BCL <jats:sub>XL</jats:sub> PROTAC was associated with an increase in the proliferation marker Ki67 and enhanced cell proliferation. Additionally, in precisioncut lung slices obtained from COPD patients, BCL <jats:sub>XL</jats:sub> PROTAC signific
AU - Devulder,JV
AU - Fenwick,PS
AU - Kolosionek,E
AU - AlSahaf,M
AU - Viola,P
AU - Lemaire,R
AU - Razdan,N
AU - Kudo,H
AU - Sinadinos,A
AU - Odqvist,L
AU - Donnelly,LE
AU - Barnes,PJ
DO - 10.1111/acel.70487
PY - 2026///
SN - 1474-9718
TI - Clearance of Senescent Cells by <scp> BCL <sub>XL</sub> </scp> <scp>PROTAC</scp> : A Novel Approach to Treat <scp>COPD</scp> ?
T2 - Aging Cell
UR - http://dx.doi.org/10.1111/acel.70487
UR - https://doi.org/10.1111/acel.70487
VL - 25
ER -