Fibrosis-related diseases carry with them a high mortality rate and their morbidity increases with age. Recent findings indicate that induced senescence in myofibroblasts can limit or reduce myocardial fibrosis, cirrhosis, and idiopathic pulmonary fibrosis, while also accelerating wound healing. However, more senescent cells are accumulated as organisms age, which exacerbates aging-related diseases. These two contradictory theories inspired us to summarize papers on the restrictive effect of senescence on fibrosis and to input the key findings into simple software that we developed to assist with data organization and presentation. In this review, we illustrate that senescent cells secrete more matrix metalloproteinases to solubilize excess collagen, while chemokines and cytokines activate immune cells to eliminate senescent cells. In the elderly, it is perhaps more effective to limit fibrosis by inducing myofibroblast senescence and then removing senescent cells that are not cleared via normal mechanisms by antisenescence therapies.

Cellular senescence decreases cell proliferation over time and is characterized by typical markers, including larger cell volume, a flattened morphology, irreversible cell cycle arrest, augmentation of senescence-associated β-galactosidase (SA-β-gal) activity and senescence-associated secretory phenotype. A variety of factors are implicated in the process of cellular aging, which mediates an organisms' lifespan. Insulin-like growth factor-1 (IGF-1) serves an essential role in regulating cell growth, division, proliferation and senescence. In the present study, the role of IGF-1 and the downstream Akt signaling pathway in rat articular chondrocyte senescence was assessed. The results of the current study demonstrated that IGF-1 promoted cellular senescence in rat articular chondrocytes via activation of SA-β-gal and the upregulation of p53 and p21 mRNA and protein levels. IGF-1 enhanced Akt phosphorylation and treatment with Akt inhibitor, MK-2206, significantly suppressed the induction of these markers. Overall, the results indicated the involvement of IGF-1 and Akt in senescence exhibited by rat articular chondrocytes.

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Endogenous homeostasis and peripheral tissue metabolism are disrupted by irregular fluctuations in activation, movement, feeding and temperature, which can accelerate negative biological processes and lead to immune reactions, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This review summarizes abnormal phenotypes in articular joint components such as cartilage, bone and the synovium, attributed to the deletion or overexpression of clock genes in cartilage or chondrocytes. Understanding the functional mechanisms of different genes, the differentiation of mouse phenotypes and the prevention of joint ageing and disease will facilitate future research.

Osteoarthritis (OA) is a degenerative joint disease which is one of the most frequent and disabling diseases encountered in elderly individuals. Leptin was unregulated significantly in OA cartilage and was regarded as a metabolic link between obesity and OA. In this study, we evaluated the effect of 10 or 100 ng/ml leptin on the ATDC5 cells. Results revealed that 10 or 100 ng/ml of leptin significantly decrease the expression of aggrecan and type II collagen mRNA and protein levels compare to control (0 ng/ml). Interestingly, sex determining region Y-box 9 mRNA and protein was down-regulated by leptin. Collagen X is a specific marker of hypertrophic and calcified chondrocyte. It has been noted that both mRNA and protein of Collagen X was significantly upregulated with leptin treatment. Meanwhile, Alcian Blue staining indicated that leptin reduces the synthesis of proteoglycan. Alizarin red S staining and alkaline phosphatase activity detection demonstrated that leptin induced cartilage nodules formation and mineralization in a dose dependent manner. We conclude that leptin slightly inhibits the proliferation of ATDC5 cells and affects cartilage-specifically marked proteins and genes. In summary, it has been suggested that leptin stimulate hypertrophic differentiation of ATDC5 cells.