title: Cellular senescence and autophagy in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
abstract: Aging is associated with impairments in homeostasis. Although aging and senescence are not equivalent, the number of senescent cells increases with aging. Cellular senescence plays important roles in tissue repair or remodeling, as well as embryonic development. Autophagy is a process of lysosomal self-degradation that maintains a homeostatic balance between the synthesis, degradation, and recycling of cellular proteins. Autophagy diminishes with aging; additionally, accelerated aging can be attributed to reduced autophagy. Cellular senescence has been widely implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease of accelerated lung aging, presumably by impairing cell repopulation and by aberrant cytokine secretion in the senescence-associated secretory phenotype. The possible participation of autophagy in the pathogenic sequence of COPD has been extensively explored. Although it has been reported that increased autophagy may induce epithelial cell death, an insufficient reserve of autophagy can induce cellular senescence in bronchial epithelial cells of COPD. Furthermore, advanced age is one of the most important risk factors for the development of idiopathic pulmonary fibrosis (IPF). Telomere shortening is found in blood leukocytes and alveolar epithelial cells from patients with IPF. Accelerated senescence of epithelial cells plays a role in IPF pathogenesis by perpetuating abnormal epithelial-mesenchymal interactions. Insufficient autophagy may be an underlying mechanism of accelerated epithelial cell senescence and myofibroblast differentiation in IPF. Herein, we review the molecular mechanisms of cellular senescence and autophagy and summarize the role of cellular senescence and autophagy in both COPD and IPF.
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: kkuwano@jikei.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: md986001@yahoo.co.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Araya
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: qqar2cxd@flute.ocn.ne.jp.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hara
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: shunske@jikei.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Minagawa
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: ntakasak@hotmail.com.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takasaka
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: saburo.ito.s55@gmail.com.
authors.forename: Saburo
authors.initials: S
authors.lastname: Ito
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: k.kpetshopboy@gmail.com.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: kat_n1@hotmail.com.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000235:genetics* / Q000502:physiology*; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000209:etiology*; D007962:Leukocytes; D011650:Pulmonary Alveoli / Q000166:cytology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology*; D059506:Telomere Shortening
chemical_list: D016207:Cytokines
keywords: Aging; Autophagy; Chronic obstructive lung disease (COPD); Idiopathic pulmonary fibrosis (IPF); Senescence