Dysregulation of the Bmi‐1/p16Ink4a pathway provokes an aging‐associated decline of submandibular gland function. Issue 4 (31st March 2015)

• Record Type: Journal Article
• Authors: Yamakoshi, Kimi; Katano, Satoshi; Iida, Mayu; Kimura, Hiromi; Okuma, Atsushi; Ikemoto‐Uezumi, Madoka; Ohtani, Naoko; Hara, Eiji; Maruyama, Mitsuo
• Is Part Of: Aging cell. Volume 14:Issue 4(2015:Aug.)
• Page Start: 616
• Page End: 624
• Publication Date: 2015-03-31
• Subjects: Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12337
• Languages: English
• ISSNs: 1474-9718

Abstract

<abstract abstract-type="main" id="acel12337-abs-0001"> <title>Summary</title> <p>Bmi‐1 prevents stem cell aging, at least partly, by blocking expression of the cyclin‐dependent kinase inhibitor p16^Ink4a. Therefore, dysregulation of the Bmi‐1/p16^Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi‐1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi‐1/p16^Ink4a pathway occurs during aging <italic>in vivo</italic>. Using real‐time <italic>in vivo</italic> imaging of p16^Ink4a expression in Bmi‐1‐KO mice, we uncovered a novel function of the Bmi‐1/p16^Ink4a pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging <italic>in vivo</italic>, leading to induction of p16^Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging‐related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly.</p> </abstract>