title: p53 Induces skin aging by depleting Blimp1+ sebaceous gland cells.
abstract: p53 is an important inducer of organismal aging. However, its roles in the aging of skin remain unclear. Here we show that mice with chronic activation of p53 develop an aging phenotype in the skin associated with a reduction of subcutaneous fat and loss of sebaceous gland (SG). The reduction in the fat layer may result from the decrease of mammalian TOR complex 1 (mTORC1) activity accompanied by elevated expression of energy expenditure genes, and possibly as compensatory effects, leading to the elevation of peroxisome proliferator-activated receptor (PPAR)γ, an inducer of sebocyte differentiation. In addition, Blimp1(+) sebocytes become depleted concomitantly with an increase in cellular senescence, which can be reversed by PPARγ antagonist (BADGE) treatment. Therefore, our results indicate that p53-mediated aging of the skin involves not only thinning through the loss of subdermal fat, but also xerosis or drying of the skin through declining sebaceous gland activity.
authors.affiliation: Division of Biological Sciences, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Section of Cell and Developmental Biology, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nakasaki
authors.affiliation: Division of Biological Sciences, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Todorova
authors.affiliation: Division of Biological Sciences, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lake
authors.affiliation: Division of Biological Sciences, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Yuan
authors.affiliation: Section of Cell and Developmental Biology, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jamora
authors.affiliation: Division of Biological Sciences, University of California, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D016922:Cellular Senescence; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017382:Reactive Oxygen Species / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000378:metabolism*; D015595:Skin Aging; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D047495:PPAR gamma; C513258:Prdm1 protein, mouse; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases