Proteoglycans in the Werner Syndrome and Aging: A Review and Perspective

Abstract

The Werner syndrome (WS), like several other “segmental progeroid syndromes,” provides a valuable system for investigating the genetic control of longevity and age-related pathology (Martin, 1978). In WS, except for short stature, symptoms develop in adult life and include graying and generalized loss of hair, juvenile cataracts, scleroderma-like changes in the skin, and high incidence of neoplasms. Epstein et al. (1966) noted that many of the changes in WS in vivo were suggestive of an impairment in the development and metabolism of connective tissue. Clinically, a prominent feature is atrophy of the skin over areas in which the subcutaneous adipose tissue is depleted, resulting in a shiny smooth skin which cannot be lifted or is actually adherent to the underlying tissue. There is usually atrophy of the underlying connective tissue, musculature and fat, and development of hyperkeratoses over the bony prominences. The hyperkeratoses often become ulcerated. WS patients show an increase in occurrence of mesenchymal type tumors such as fibroliposarcomas, osteogenic sarcomas, hemangiolipomas and menigiomas. Japanese researchers (Tonkunaga, et al., 1975; Goto and Murata, 1978; Zebrower et al., 1984) have identified another connective tissue-related clinical characteristic: excessive excretion of hyaluronic acid in urine. Although these clinical manifestations are reminiscent of the aging process, there is still uncertainty as to whether this syndrome is truly a caricature of aging. Part of this uncertainty arises from the paucity of information concerning the molecular events associated with aging at the tissue and cell level. More specifically, little is known about those changes that take place within specific connective tissues of patients with the Werner syndrome.