p16INK4A mediates age-related changes in mesenchymal stem cells derived from human dental pulp through the DNA damage and stress response

Publication date: November–December 2014 Source:Mechanisms of Ageing and Development, Volumes 141–142 Author(s): Xingmei Feng , Jing Xing , Guijuan Feng , Dan Huang , Xiaohui Lu , Suzhe Liu , Wei Tan , Liren Li , Zhifeng Gu Mesenchymal stem cells derived from human dental pulp (DP-MSCs) are characterized by self-renewal and multi-lineage differentiation, which play important roles in regenerative medicine. Autologous transfers, as non-immunogenic, constitute the safest approach in cellular transplantations. However, their use may be limited by age-related changes. In the study, we compared DP-MSCs isolated from human in five age groups: 5–12y, 12–20y, 20–35y, 35–50y, and >50y. We tested the effect of age on proliferation, differentiation, senescence-associated β-galactosidase (SA-β-gal), cell cycle and programmed cell death. DP-MSCs showed characteristics of senescence as a function of age. Meanwhile, the expression of p16INK4A and γ-H2A.X significantly increased with age, whereas heat shock protein 60 (HSP60) was decreased in the senescent DP-MSCs. Reactive oxygen species (ROS) staining showed the number of ROS-stained cells and the DCFH fluorescent level were higher in the aged group. Further we examined the senescence of DP-MSCs after modulating p16INK4A signaling. The results indicated the dysfunction of DP-MSCs was reversed by p16INK4A siRNA. In summary, our study indicated p16INK4A pathway may play a critical role in DP-MSCs age-relate...
Source: Mechanisms of Ageing and Development - Category: Geriatrics Source Type: research