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Clinical and Basic Biology of Werner Syndrome, the Model Disease of Human Aging

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Aging Mechanisms II

Abstract

Werner syndrome is an autosomal recessive genetic disorder first described in 1904 by Otto Werner, a German ophthalmologist. It is considered the representative progeroid syndrome because various signs of aging, such as gray hair, cataracts, diabetes, and skin ulcers, appear after puberty. The onset of the disease begins in the 20s or 30s, leading to diabetes and atherosclerosis, and death in mid-50s due to myocardial infarction or malignant tumors. The number of patients in Japan is estimated to be between 700 and 2000, and 60% of the world’s reports are from Japan, suggesting that this accelerated aging disease is more common in Japan. The cause of Werner syndrome was identified in 1996 as a mutation in the WRN gene, a RECQ helicase located in chromosome 8. Since then, various studies have shown that the syndrome is associated with decreased DNA damage repair and genomic instability, shortened telomeres, chronic inflammation due to cellular senescence- and senescence-associated secretory phenotype (SASP), decreased mitochondrial function and accumulation of oxidative stress, stem cell senescence, and epigenetic changes. While most premature aging syndromes occur in childhood and involve a growth and developmental disorder, only Werner syndrome occurs after normal growth and puberty, suggesting that this syndrome is a model of human aging. The elucidation of the pathogenesis and molecular mechanisms of this disease and the development of a treatment strategy are expected to lead to the elucidation of the pathogenesis of general human aging and of aging-related diseases such as diabetes and malignant tumors.

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Authors and Affiliations

  1. Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan

    Yoshiro Maezawa, Masaya Koshizaka, Hisaya Kato & Koutaro Yokote

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  1. Yoshiro Maezawa
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  2. Masaya Koshizaka
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  3. Hisaya Kato
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  4. Koutaro Yokote
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Correspondence to Koutaro Yokote .

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  1. Fukuoka International University of Health and Welfare, Fukuoka, Japan

    Nozomu Mori

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Maezawa, Y., Koshizaka, M., Kato, H., Yokote, K. (2022). Clinical and Basic Biology of Werner Syndrome, the Model Disease of Human Aging. In: Mori, N. (eds) Aging Mechanisms II . Springer, Singapore. https://doi.org/10.1007/978-981-16-7977-3_2

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