Down-regulation of a forkhead transcription factor, FOXO3a, accelerates cellular senescence in human dermal fibroblasts

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Vol. 60; no. 1; p. 4
• Main Authors: Kyoung Kim, Hyun, Kyoung Kim, Yu, Song, In-Hwan, Baek, Suk-Hwan, Lee, Seung-Rock, Hye Kim, Jung, Kim, Jae-Ryong
• Format: Journal Article
• Language: English
• Published: United States 01.01.2005
• Subjects: Cells, Cultured; Cellular Senescence - physiology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Down-Regulation; Fibroblasts - physiology; Forkhead Box Protein O1; Forkhead Transcription Factors; Humans; Phenotype; RNA, Small Interfering - biosynthesis; Skin - cytology; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 1079-5006
• DOI: 10.1093/gerona/60.1.4

The signaling pathway of insulin/insulin-like growth factor/phosphatidylinositol-3 kinase/Akt/forkhead transcription factors is known to control life span and senescence in organisms ranging from yeast to mice. The FOXO family of forkhead transcription factors, FOXO1, FOXO3a, and FOXO4, play a critical role in this signal transduction pathway. However, the impact of FOXO3a activation on life span of primary cultured human dermal fibroblasts (HDFs) is unknown. To investigate the role of FOXO3a in the regulation of cellular senescence, we prepared FOXO3a-siRNA stable HDFs. We found that the down-regulation of FOXO3a RNA and protein in HDFs induced many senescent phenotypes, including changes in cell morphology, increases in population doubling times, senescence-associated beta-galactosidase staining and the cellular reactive oxygen species, and up-regulation of p53/p21 protein expression. Our data provide evidence of the key role of FOXO3a transcription factor as a mediator of cellular senescence in HDFs, and suggest that the mechanism of senescence is conserved in HDFs.