Increased procoagulant activity in cultured fibroblasts from progeria and Werner's syndromes of premature ageing.

Abstract

BIOLOGICAL ageing undoubtedly involves a number of complex physiological and biochemical factors but it is increasingly evident that the cultured human fibroblast will help to elucidate the fundamental nature of this process. These cells have a finite replicative lifespan that is inversely related to the age of the donor1–3. Moreover, physiological rather than chronological age is a critical determinant, since cultured fibroblasts from the progeria and Werner's syndromes of premature ageing have significantly reduced growth potential compared with normal, age-matched controls3–5. Although the decreased replicative ability of cells may help to explain some of the features of progeria and Werner's syndrome, such as stunting of growth and impaired wound healing ability, it does not explain other pathological concomitants of these disorders. In particular, an explanation is needed for the premature appearance of severe atherothrombotic disease6,7. Tt has been shown that human fibroblasts contain a potent procoagulant activity called ‘tissue factor’ (TF)8. TF has the capacity to activate the extrinsic clotting mechanism through factor VII, eventually leading to thrombin generation which then promotes clot formation through fibrinogen8,9. We report here that skin fibroblasts derived from subjects with progeria and Werner's syndrome have markedly elevated levels of TF compared with controls.