Werner syndrome: a model for sarcopenia due to accelerated aging

Abstract

Werner syndrome (WS) is a rare inheritable progeroid syndrome caused by a mutation in the WRN gene. Although WS has been described as a characteristic appearance of very slender extremities with a stocky trunk, few studies have investigated the loss of muscle mass, fat mass distribution (body composition), and mobility according to age and sex. Therefore, the aim of this study was to precisely describe the body composition in WS. Nine Japanese patients with WS (four males and five females; mean age 48±8.8 years) were recruited. Body composition was examined by dual-energy X-ray absorptiometry and computed tomography (CT). The hand grip strength and mobility were evaluated using the two-step test, stand-up test and 25-question geriatric locomotive function scale. The mean skeletal muscle index (SMI) was 4.0±0.6 kg/m. SMI of all patients met the criteria of sarcopenia, even though some patients were aged < 40 years. All patients also showed deceased mobility. In conclusion, these results indicate that all patients with WS, even those aged < 40 years, had already lost muscle mass to the level of sarcopenia. Continued research on sarcopenia in WS might facilitate the discovery of novel mechanisms and development of new treatment strategies for sarcopenia.

Diabetes mellitus coexisted with progeria: a case report of atypical Werner syndrome with novel LMNA mutations and literature review

“…The possible mechanisms of insulin resistance in WS patients (both CWS and AWS) include reduced insulin receptors in fat cells, loss of signal transduction after the binding of normal insulin to normal receptors, and defected post-receptor step [11,19]. The physical activity reduced for sarcopenia in WS patients may be one cause for accumulation of visceral fat, resulting in insulin resistance [20]. In addition, dysregulation of adipocytokine may be another mechanism for the development of DM in WS patients.…”

Management guideline for Werner syndrome 2020. 2. Sarcopenia associated with Werner syndrome

“…A literature search on the relationship between Werner syndrome and skeletal muscle yielded only one article reported from Japan in 2017 4 . According to that report, nine patients with Werner syndrome (four men and five women) with the mean age of 48 ± 8.8 years (range: 39–60 years) underwent a diagnostic test for sarcopenia based on indexes including decreases in the appendicular skeletal muscle mass index and the grip strength using the diagnostic criteria for sarcopenia (appendicular skeletal muscle index obtained by dual‐energy X‐ray absorptiometry [appendicular skeletal muscle mass, kg/body height, m 2 : <7.0 kg/m 2 [male], <5.4 kg/m 2 [female] and grip strength: <26 kg [male], <18 kg [female]) 5 suggested by Asian Working Group for Sarcopenia.…”

Investigator‐initiated clinical study of a functional peptide, SR‐0379, for limb ulcers of patients with Werner syndrome as a pilot study

“…Werner syndrome is a very rare autosomal recessive disorder caused by the WRN gene, which encodes a RecQ DNA helicase. Patients with Werner syndrome have several major complications, including juvenile bilateral cataracts, diabetes, dyslipidemia, atherosclerosis, malignancy and refractory leg ulcers . Among them, the incidence of severe leg ulcers markedly reduces patient activity and quality of life.…”

“…Patients with Werner syndrome have several major complications, including juvenile bilateral cataracts, diabetes, dyslipidemia, atherosclerosis, malignancy and refractory leg ulcers. [3][4][5][6] Among them, the incidence of severe leg ulcers markedly reduces patient activity and quality of life. Severe leg ulcers are usually associated with diabetes or ischemia; however, Werner syndrome is also characterized by delayed wound healing, which involves thin connective tissues, physiological overpressure by bone transformation and delayed skin fibroblast cell growth.…”