Age-dependent changes in protein incorporation into collagen-rich tissues of mice by in vivo pulsed SILAC labelling
Yoanna Ariosa-Morejon,
Alberto Santos,
Roman Fischer,
Simon Davis,
Philip Charles,
Rajesh Thakker,
Angus KT Wann,
Tonia L Vincent
Affiliations
Yoanna Ariosa-Morejon
Kennedy Institute of Rheumatology, Arthritis Research UK Centre for OA Pathogenesis, University of Oxford, Oxford, United Kingdom
Alberto Santos
Big Data Institute, Li-Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom; Center for Health Data Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, United Kingdom
Collagen-rich tissues have poor reparative capacity that predisposes to common age-related disorders such as osteoporosis and osteoarthritis. We used in vivo pulsed SILAC labelling to quantify new protein incorporation into cartilage, bone, and skin of mice across the healthy life course. We report dynamic turnover of the matrisome, the proteins of the extracellular matrix, in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed changes in epigenetic modulators across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGFβ in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several pathways were implicated in age-related disease. Fewer changes were observed for skin. This methodology provides dynamic protein data at a tissue level, uncovering age-related molecular changes that may predispose to disease.
