Abstract
Although aging represents the most important epidemiologic risk factor for fibrotic disease, the reasons for this are incompletely understood. Excess collagen deposition in tissues is the sine qua non of tissue fibrosis and can be viewed as an imbalance between collagen production and collagen degradation. Yet we still lack a detailed understanding of the changes that take place during development, maturation, and aging in extracellular matrix (ECM) dynamics. Resolution of fibrosis is impaired in aging, and this impairment may explain why age is the most important risk factor for fibrotic diseases, such as idiopathic pulmonary fibrosis. However, ECM dynamics and impaired resolution of fibrosis in aging remain understudied. Here we show that cell-mediated collagen uptake and degradation are diminished in aged animals and this finding correlates with downregulation of the collagen endocytic receptor mannose receptor, C-type 2 (Mrc2). We identify myeloid zinc finger-1 as a potentially novel transcriptional regulator of Mrc2, and both this transcription factor and Mrc2 are downregulated in multiple tissues and organisms in an age-dependent manner. Thus, cell-mediated degradation of collagen is an essential process that promotes resolution of fibrosis, and impairment in this process contributes to age-related fibrosis.
Highlights
IntroductionGenetic disorders of telomere maintenance that represent a form of premature aging have been highly associated with fibrotic disease, in particular pulmonary fibrosis [2]
Advanced age is a major risk factor for organ fibrosis, including lung fibrosis [1]
Because collagen content was higher in mature mice but transcript levels were lower, we reasoned that the age-associated accumulation of collagen may result from a dysregulation of collagen degradation pathways
Summary
Genetic disorders of telomere maintenance that represent a form of premature aging have been highly associated with fibrotic disease, in particular pulmonary fibrosis [2]. Despite these widely recognized associations, the underlying mechanism that links aging to the development of pulmonary fibrosis is incompletely understood [3]. It is generally accepted that many injuries which may cause scarring in an adult will instead cause scarless healing in a developing organism [4]. In utero surgery generally does not produce scar tissue whereas the same surgery in a child or adult does produce scarring [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
