Abstract
Both tendon injuries and tendinopathies, particularly rotator cuff tears, increase with tendon aging. Tendon stem cells play important roles in promoting tendon growth, maintenance, and repair. Aged tendons show a decline in regenerative potential coupled with a loss of stem cell function. Recent studies draw attention to aging primarily a disorder of stem cells. The micro-environment (“niche”) where stem cells resided in vivo provides signals that direct them to metabolize, self-renew, differentiate, or remain quiescent. These signals include receptors and secreted soluble factors for cell-cell communication, extracellular matrix, oxidative stress, and vascularity. Both intrinsic cellular deficits and aged niche, coupled with age-associated systemic changes of hormonal and metabolic signals can inhibit or alter the functions of tendon stem cells, resulting in reduced fitness of these primitive cells and hence more frequent injuries and poor outcomes of tendon repair. This review aims to summarize the biological changes of aged tendons. The biological changes of tendon stem cells in aging are reviewed after a systematic search of the PubMed. Relevant factors of stem cell aging including cell-intrinsic factors, changes of microenvironment, and age-associated systemic changes of hormonal and metabolic signals are examined, with findings related to tendon stem cells highlighted when literature is available. Future research directions on the aging mechanisms of tendon stem cells are discussed. Better understanding of the molecular mechanisms underlying the functional decline of aged tendon stem cells would provide insight for the rational design of rejuvenating therapies.
Highlights
Reviewed by: Atsushi Asakura, University of Minnesota Twin Cities, United States Hakan Darici, Istinye University, Turkey
This review aims to summarize the biological changes of aged tendons
While there was no change in the rate of blood flow in the flexor tendons with age in a rabbit study (Landi et al, 1983), there was a significant decrease in blood flow in the intratendinous region of rotator cuff of elderly subjects compared with younger subjects (Funakoshi et al, 2010)
Summary
Reviewed by: Atsushi Asakura, University of Minnesota Twin Cities, United States Hakan Darici, Istinye University, Turkey. The micro-environment (“niche”) where stem cells resided in vivo provides signals that direct them to metabolize, self-renew, differentiate, or remain quiescent These signals include receptors and secreted soluble factors for cellcell communication, extracellular matrix, oxidative stress, and vascularity. Rudzki et al (2008) reported a significant decrease in blood flow in intact supraspinatus tendon in asymptomatic subjects older than 40 years compared with younger subjects after exercise Nontendinous tissues such as fatty and cartilaginous tissues as well as calcification were reported in aged tendons in both animal models and human (Iagnocco et al, 2013; Zhang and Wang, 2015; Gehwolf et al, 2016; Wood and Brooks, 2016; Zaseck et al, 2016). The cell number decreased; tenocyte dedifferentiated and senescent; and their proliferation and metabolic activity reduced with aging (Ippolito et al, 1980; Josa and Kannus, 1997; Tsai et al, 2011; Dunkman et al, 2013; Yu et al, 2013)
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