Studying Werner syndrome to elucidate mechanisms and therapeutics of human aging and age-related diseases

TY - JOUR

T1 - Studying Werner syndrome to elucidate mechanisms and therapeutics of human aging and age-related diseases

AU - Lautrup, Sofie

AU - Caponio, Domenica

AU - Cheung, Hoi Hung

AU - Piccoli, Claudia

AU - Stevnsner, Tinna

AU - Chan, Wai Yee

AU - Fang, Evandro F.

PY - 2019/6

Y1 - 2019/6

N2 - Aging is a natural and unavoidable part of life. However, aging is also the primary driver of the dominant human diseases, such as cardiovascular disease, cancer, and neurodegenerative diseases, including Alzheimer’s disease. Unraveling the sophisticated molecular mechanisms of the human aging process may provide novel strategies to extend ‘healthy aging’ and the cure of human aging-related diseases. Werner syndrome (WS), is a heritable human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. As a classical premature aging disease, etiological exploration of WS can shed light on the mechanisms of normal human aging and facilitate the development of interventional strategies to improve healthspan. Here, we summarize the latest progress of the molecular understandings of WRN protein, highlight the advantages of using different WS model systems, including Caenorhabditis elegans, Drosophila melanogaster and induced pluripotent stem cell (iPSC) systems. Further studies on WS will propel drug development for WS patients, and possibly also for normal age-related diseases.

AB - Aging is a natural and unavoidable part of life. However, aging is also the primary driver of the dominant human diseases, such as cardiovascular disease, cancer, and neurodegenerative diseases, including Alzheimer’s disease. Unraveling the sophisticated molecular mechanisms of the human aging process may provide novel strategies to extend ‘healthy aging’ and the cure of human aging-related diseases. Werner syndrome (WS), is a heritable human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. As a classical premature aging disease, etiological exploration of WS can shed light on the mechanisms of normal human aging and facilitate the development of interventional strategies to improve healthspan. Here, we summarize the latest progress of the molecular understandings of WRN protein, highlight the advantages of using different WS model systems, including Caenorhabditis elegans, Drosophila melanogaster and induced pluripotent stem cell (iPSC) systems. Further studies on WS will propel drug development for WS patients, and possibly also for normal age-related diseases.

KW - Aging

KW - DNA repair

KW - Hallmarkers of aging

KW - Mitophagy

KW - NAD

KW - Premature aging

KW - Werner syndrome

KW - VITAMIN-C

KW - LIFE-SPAN

KW - SYNDROME FIBROBLASTS

KW - DNA-DAMAGE

KW - DOWN-REGULATION

KW - SYNDROME PROTEIN

KW - ELEGANS WRN HELICASE

KW - NUCLEAR-LOCALIZATION

KW - GENE

KW - NAD(+)

KW - STEM-CELL MODEL

UR - http://www.scopus.com/inward/record.url?scp=85060351655&partnerID=8YFLogxK

U2 - 10.1007/s10522-019-09798-2

DO - 10.1007/s10522-019-09798-2

M3 - Review

C2 - 30666569

AN - SCOPUS:85060351655

SN - 1389-5729

VL - 20

SP - 255

EP - 269

JO - Biogerontology

JF - Biogerontology

IS - 3

ER -