Category Cytokines MMPs TIMPs KGF VEGF IL-6 MCP-1 MMP-1 MMP-2 MMP-3 TIMP-1 TIMP-2 Fr/Fp Fr/Fp Fr/Fp Fr/Fp Fr/Fp Fr/Fp Fp Fr Fp Fr Fp Fr Fp Fr Fp Fr Fp Fr Fp Fr Fp Fr Fp Fr Fr/Fp Fr/Fp Fr/Fp Figure 3. Secretion of KGF by Fp and Fr as a function of donor’s age. Evolution of secretion was estimated by linear regression in a cohort of 16 different pairs of Fp and Fr obtained from independent donors, ranging from 19 to 74 years old. Secretion of KGF was quantified. Values are expressed in pg/ml per 105 cells. (A) KGF secretion by Fp samples. (B) KGF secretion by Fr samples. (C) KGF secretion ratio [Fr/Fp]. doi:10.1371/journal.pone.0004066.g003 Age-dependent capacity of Fp and Fr to contract a collagen gel To investigate differences in the capacity of Fp and Fr from young (19 yr, 21 yr, and 26 yr) and old (57 yr, 62 yr, and 74 yr) donors to contract a collagen gel, cells were embedded into type I collagen, and the diameter of dermal equivalents (lattices) was measured from day 1 to day 4 after culture initiation. In the young age group, the diameters of the lattices containing Fr cells were significantly lower than those containing Fp cells at each time point of the study (p,0.05), indicating a higher rate of lattice Table 1. Secretion profiles of cytokines, MMPs and TIMPs by Fp and Fr as a function of donor’s age. Specific proteins Fibroblasts and ratio Evolution with age of the secretion profiles of Fp and Fr was analyzed by linear regression on a cohort of 16 different pairs of fibroblast samples obtained from independent donors, ranging from 19 to 74 years old. Secretion level of specific proteins was considered as significantly modulated with age when the correlation coefficient (R) was found .0.5 (in absolute value) and p,0.05 (*). doi:10.1371/journal.pone.0004066.t001 PLoS ONE | www.plosone.org 6 December 2008 | Volume 3 | Issue 12 | e4066 Fp and Fr in Skin Aging R *0.599 0.075 *0.657 0.38907 0.105 0.41096 0.162 0.04 0.114 0.176 *0.514 *0.615 *0.531 0.258 *0.690 *0.533 0.158 0.479 *0.527 0.095 *0.686 *0.622 0.096 *0.609 *0.536 0.098 0.451 p-value *0.014 0.782 *0.006 0.1364 0.698 0.1138 0.55 0.883 0.674 0.515 *0.042 *0.011 *0.034 0.335 *0.003 *0.034 0.559 0.0601 *0.036 0.726 *0.003 *0.010 0.724 *0.012 *0.032 0.719 0.079 Regulation Up-regulation No regulation Up-regulation No regulation No regulation No regulation No regulation Down-reguation Up-regulation No regulation Up-regulation No regulation Up-regulation No regulation Up-regulation No regulation Up-regulation No regulation