Tobacco
smoke-induced accelerated cell senescence has been implicated in the pathogenesis of
chronic obstructive pulmonary disease (
COPD). Cell senescence is accompanied by the accumulation of damaged cellular components suggesting that in
COPD, inhibition of autophagy may contribute to cell senescence. Here we look at whether autophagy contributes to cigarette
smoke extract (CSE) - induced cell senescence of primary human bronchial epithelial cells (HBEC), and further evaluate p62 and ubiquitinated
protein levels in lung homogenates from
COPD patients. We demonstrate that CSE transiently induces activation of autophagy in HBEC, followed by accelerated cell senescence and concomitant accumulation of p62 and
ubiquitinated proteins. Autophagy inhibition further enhanced accumulations of p62 and
ubiquitinated proteins, resulting in increased senescence and senescence-associated secretory phenotype (SASP) with
interleukin (IL)-8 secretion. Conversely, autophagy activation by Torin1, a
mammalian target of rapamycin (mTOR inhibitor), suppressed accumulations of p62 and
ubiquitinated proteins and inhibits cell senescence. Despite increased baseline activity, autophagy induction in response to CSE was significantly decreased in HBEC from
COPD patients. Increased accumulations of p62 and
ubiquitinated proteins were detected in lung homogenates from
COPD patients. Insufficient autophagic clearance of damaged
proteins, including
ubiquitinated proteins, is involved in accelerated cell senescence in
COPD, suggesting a novel protective role for autophagy in the tobacco
smoke-induced senescence-associated
lung disease,
COPD.