title: SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin.
abstract: Mesenchymal stem cells (MSCs) senescence is an age-related process that impairs the capacity for tissue repair and compromises the clinical use of autologous MSCs for tissue regeneration. Here, we describe the effects of SIRT1, a NAD(+)-dependent deacetylase, on age-related MSCs senescence. Knockdown of SIRT1 in young MSCs induced cellular senescence and inhibited cell proliferation whereas overexpression of SIRT1 in aged MSCs reversed the senescence phenotype and stimulated cell proliferation. These results suggest that SIRT1 plays a key role in modulating age-induced MSCs senescence. Aging-related proteins, P16 and P21 may be downstream effectors of the SIRT1-mediated anti-aging effects. SIRT1 protected MSCs from age-related DNA damage, induced telomerase reverse transcriptase (TERT) expression and enhanced telomerase activity but did not affect telomere length. SIRT1 positively regulated the expression of tripeptidyl peptidase 1 (TPP1), a component of the shelterin pathway that protects chromosome ends from DNA damage. Together, the results demonstrate that SIRT1 quenches age-related MSCs senescence by mechanisms that include enhanced TPP1 expression, increased telomerase activity and reduced DNA damage.
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Yinchuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Lihan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Dexing
authors.initials: D
authors.lastname: Hu
authors.affiliation: Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China ; Key Lab of Cardiovascular Disease, Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Jian'an
authors.initials: J
authors.lastname: Wang
keywords: SIRT1; TPP1; aging; mesenchymal stem cells; senescence; shelterin; telomerase