Werner syndrome: a model for sarcopenia due to accelerated aging

Yamaga, Masaya; Takemoto, Minoru; Shoji, Mayumi; Sakamoto, Kenichi; Yamamoto, Masashi; Ishikawa, Takahiro; Koshizaka, Masaya; Maezawa, Yoshiro; Kobayashi, Kazuki; Yokote, Koutaro

doi:10.18632/aging.101265

Cited by 14 publications

(15 citation statements)

References 37 publications

(40 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Yan

Sun

et al. 2019

Endocr J

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Werner syndrome (WS) is a rare, adult-onset progeroid syndrome. Classic WS is caused by WRN mutation and partial atypical WS (AWS) is caused by LMNA mutation. A 19-year-old female patient with irregular menstruation and hyperglycemia was admitted. Physical examination revealed characteristic faces of progeria, graying and thinning of the hair scalp, thinner and atrophic skin over the hands and feet, as well as lipoatrophy of the extremities, undeveloped breasts at Tanner stage 3, and short stature. The patient also suffered from severe insulin-resistant diabetes mellitus, hyperlipidemia, fatty liver, and polycystic ovarian morphology. Possible WS was considered and both WRN and LMNA genes were analyzed. A novel missense mutation p.L140Q (c.419T>A) in the LMNA gene was identified and confirmed the diagnosis of AWS. Her father was a carrier of the same mutation. We carried out therapy for lowering blood glucose and lipid and improving insulin resistance, et al. The fasting glucose, postprandial glucose and triglyceride level was improved after treatment for 9 days. Literature review of AWS was performed to identify characteristics of the disease. Diabetes mellitus is one of the clinical manifestations of WS and attention must give to the differential diagnosis. Gene analysis is critical in the diagnosis of WS. According to the literature, classic and atypical WS differ in incidence, pathogenic gene, and clinical manifestations. Characteristic dermatological pathology may be significantly more important for the initial identification of AWS. Early detection, appropriate treatments, and regular follow-up may improve prognosis and survival of WS patients.

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Section: Discussionmentioning

confidence: 99%

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

Yan

Sun

et al. 2019

Endocr J

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“…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.…”

Section: Sarcopenia In Patients With Werner Syndromementioning

confidence: 99%

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

Kuzuya

Takemoto

Kubota

et al. 2020

Geriatr. Gerontol. Int.

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Aim Sarcopenia is defined as a condition that combines decreased skeletal muscle mass with weakness or decreased physical function. It is well known that in older adults, the presence of sarcopenia is a risk of frailty, falls and physical dysfunction. Patients with Werner syndrome are characterized by visceral fat accumulation and thin limbs, but the prevalence of sarcopenia in patients with Werner syndrome has not been investigated. Methods A literature search was conducted using Werner syndrome and skeletal muscle as keywords. We also analyzed data from our 7 Werner syndrome patients. Results A literature search on the relationship between Werner syndrome and skeletal muscle yielded only one article reported from Japan. According to this paper, a decrease in skeletal muscle mass (appendicular skeletal muscle index) was observed in all 9 Werner syndromes investigated. On the other hand, in our 7 Werner syndrome patients, their appendicular skeletal muscle indexes were below the standard value except for one male patient who had continued resistance exercise. Conclusion The decrease in skeletal muscle mass frequently occurs in patients with Werner syndrome. However, resistance exercise may prevent the appearance of sarcopenia and requires early intervention in patients with Werner syndrome. Geriatr Gerontol Int 2021; 21: 139–141.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Nakagami

Sugimoto

Ishikawa

et al. 2019

Geriatr. Gerontol. Int.

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Aim An investigator‐initiated clinical study was carried out to evaluate the therapeutic potency of SR‐0379 for the treatment of leg ulcers in patients with Werner syndrome. Methods A multicenter, open‐label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and <6 cm in diameter. Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR‐0379 (0.1%) was sprayed on skin ulcers once per day for 4 weeks. Efficacy was evaluated by determining the rate of wound size reduction as a primary end‐point at 4 weeks after the first treatment compared with the pretreatment wound size. As secondary end‐points, the DESIGN‐R score index, the 50% wound size reduction ratio, time to wound closure and quantification of wound bacteria were also evaluated. The safety of SR‐0379 was evaluated during the study period. Results The reduction rate of ulcer size treated with 0.1% SR‐0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4) and 35.70% (mean) in the diabetic ulcers group (n = 4), respectively. The DESIGN‐R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two mild adverse events were reported in two patients, and causal relationships were denied in any events. Conclusion Treatment with SR‐0379 was safe, well‐tolerated, and effective for leg ulcers of both Werner syndrome and diabetes patients. Geriatr Gerontol Int 2019; 19: 1118–1123.

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Werner syndrome: a model for sarcopenia due to accelerated aging

Cited by 14 publications

References 37 publications

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

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

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

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

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