Advanced glycation end-product crosslinking in ageing skeletal tissues
Helen Birch
Institute of Orthopaedics and Musculoskeletal Science
UCL, London
[email protected]
Increasing age is a well-known major risk factor for tendon injuries and although tendon injuries are not life threatening, they cause considerable pain and disability. The WHO has recognised the promotion of physical activity as one of the greatest potentials to achieve gains in health in older age, highlighting the importance of musculoskeletal fitness. Despite this, relatively little is understood about the ageing process and the underlying changes that result in a decline in the functional ability of tendons.
The turnover of collagen, the predominant protein in tendon, is remarkably slow and half-life increases further with increasing chronological age. The long-lived nature of tendon collagen renders it susceptible to the formation of advanced glycation end-products (AGE) following attack by reactive carbonyl groups on sugars such as glucose (glycation). A series of spontaneous chemical re-arrangements and further reactions results in AGE crosslinks, the most abundant of which is thought to be glucosepane. Our current research is focused on understanding the formation, extent and location of AGE crosslinks, particularly glucosepane, in type I collagen and the effect these crosslinks have on the mechanical and biological properties of tendon. Our studies have shown that glucosepane levels increase with increasing age in human tendon. The sites we have identified as preferential sites for glucosepane formation overlap with other important bioactive interactions sites.
The author has no financial interests to disclose.
Helen Birch
Institute of Orthopaedics and Musculoskeletal Science
UCL, London
[email protected]
Increasing age is a well-known major risk factor for tendon injuries and although tendon injuries are not life threatening, they cause considerable pain and disability. The WHO has recognised the promotion of physical activity as one of the greatest potentials to achieve gains in health in older age, highlighting the importance of musculoskeletal fitness. Despite this, relatively little is understood about the ageing process and the underlying changes that result in a decline in the functional ability of tendons.
The turnover of collagen, the predominant protein in tendon, is remarkably slow and half-life increases further with increasing chronological age. The long-lived nature of tendon collagen renders it susceptible to the formation of advanced glycation end-products (AGE) following attack by reactive carbonyl groups on sugars such as glucose (glycation). A series of spontaneous chemical re-arrangements and further reactions results in AGE crosslinks, the most abundant of which is thought to be glucosepane. Our current research is focused on understanding the formation, extent and location of AGE crosslinks, particularly glucosepane, in type I collagen and the effect these crosslinks have on the mechanical and biological properties of tendon. Our studies have shown that glucosepane levels increase with increasing age in human tendon. The sites we have identified as preferential sites for glucosepane formation overlap with other important bioactive interactions sites.
The author has no financial interests to disclose.
