期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 72, 期 9, 页码 1196-1200出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glx091
关键词
Cdc42; CpG methylation; Aging biomarker; Cardiovascular disease; Myocardial infarction
资金
- Emmy Noether Grant (DFG)
- Deutsche Forschungsgemeinschaft [SFB 1074, SFB1149, KFO 142]
- Excellence-Initiative of the Baden-Wurttemberg-Foundation
- BMBF
- Edward P. Evans Foundation
- National Institute of Health [HL134617, AG040118, DK104814, AG05065]
The small RhoGTPase Cdc42 is mechanistically linked to aging of multiple tissues and to rejuvenation of hematopoietic stem cells in mice. However, data validating Cdc42 activity and expression as biomarker for aging in humans are still missing. Here, we hypothesized that Cdc42 might serve as a novel biomarker of aging in older adults and therefore we determined Cdc42 activity and expression levels in peripheral blood cells from a cohort of 196 donors. We investigated the association of these parameters with both chronological and biological aging. We also tested in this cohort of older adults a recently published algorithm determining chronological age based on DNA methylation profiles. A positive correlation with chronological age was found for both the level of Cdc42 mRNA and the level of active Cdc42 protein (the GTP bound form). Notably, the level of Cdc42 mRNA as well as total protein showed a specific strong association to cardiovascular disease and Cdc42 mRNA levels also to a history of myocardial infarction. In summary, these data validate Cdc42 as a blood biomarker of both chronological aging as well as aging-associated diseases like cardiovascular disease and myocardial infarction.
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