The Fountain of Youth by Targeting Senescent Cells?

被引:113
作者
de Keizer, Peter L. J. [1 ]
机构
[1] Erasmus Univ, Med Ctr Rotterdam, Rotterdam, Netherlands
关键词
ONCOGENE-INDUCED SENESCENCE; HEMATOPOIETIC STEM-CELLS; FORKHEAD BOX O; SECRETORY PHENOTYPE; DNA-REPAIR; CELLULAR SENESCENCE; IN-VIVO; TRANSCRIPTION FACTORS; PEPTIDE INHIBITOR; BREAST-CANCER;
D O I
10.1016/j.molmed.2016.11.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner. This review argues that to fulfill this niche, cell-penetrating peptides may provide promising therapeutics. As a candidate approach, the author also highlights the potential of targeting individual FOXO signaling pathways to combat senescence and stimulate tissue rejuventaion.
引用
收藏
页码:6 / 17
页数:12
相关论文
共 95 条
[1]
Chemokine signaling via the CXCR2 receptor reinforces senescence [J].
Acosta, Juan C. ;
O'Loghlen, Ana ;
Banito, Ana ;
Guijarro, Maria V. ;
Augert, Arnaud ;
Raguz, Selina ;
Fumagalli, Marzia ;
Da Costa, Marco ;
Brown, Celia ;
Popov, Nikolay ;
Takatsu, Yoshihiro ;
Melamed, Jonathan ;
di Fagagna, Fabrizio d'Adda ;
Bernard, David ;
Hernando, Eva ;
Gil, Jesus .
CELL, 2008, 133 (06) :1006-1018
[2]
An Immunohistochemistry Study of Tissue Bcl-2 Expression and Its Serum Levels in Breast Cancer Patients [J].
Alireza, Andalib ;
Raheleh, Shokohi ;
Abbass, Rezaei ;
Mojgan, Mokhtari ;
Mohamadreza, Mohageri ;
Gholamreza, Mohageri ;
Shadi, Babazadeh .
RECENT ADVANCES IN CLINICAL ONCOLOGY, 2008, 1138 :114-120
[3]
Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency [J].
Baker, Darren J. ;
Perez-Terzic, Carmen ;
Jin, Fang ;
Pitel, Kevin ;
Niederlaender, Nicolas J. ;
Jeganathan, Karthik ;
Yamada, Satsuki ;
Reyes, Santiago ;
Rowe, Lois ;
Hiddinga, H. Jay ;
Eberhardt, Norman L. ;
Terzic, Andre ;
van Deursen, Jan M. .
NATURE CELL BIOLOGY, 2008, 10 (07) :825-836
[4]
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan [J].
Baker, Darren J. ;
Childs, Bennett G. ;
Durik, Matej ;
Wijers, Melinde E. ;
Sieben, Cynthia J. ;
Zhong, Jian ;
Saltness, Rachel A. ;
Jeganathan, Karthik B. ;
Verzosa, Grace Casaclang ;
Pezeshki, Abdulmohammad ;
Khazaie, Khashayarsha ;
Miller, Jordan D. ;
van Deursen, Jan M. .
NATURE, 2016, 530 (7589) :184-+
[5]
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders [J].
Baker, Darren J. ;
Wijshake, Tobias ;
Tchkonia, Tamar ;
LeBrasseur, Nathan K. ;
Childs, Bennett G. ;
van de Sluis, Bart ;
Kirkland, James L. ;
van Deursen, Jan M. .
NATURE, 2011, 479 (7372) :232-U112
[6]
Cell-Autonomous Progeroid Changes in Conditional Mouse Models for Repair Endonuclease XPG Deficiency [J].
Barnhoorn, Sander ;
Uittenboogaard, Lieneke M. ;
Jaarsma, Dick ;
Vermeij, Wilbert P. ;
Tresini, Maria ;
Weymaere, Michael ;
Menoni, Herve ;
Brandt, Renata M. C. ;
de Waard, Monique C. ;
Botter, Sander M. ;
Sarker, Altaf H. ;
Jaspers, Nicolaas G. J. ;
van der Horst, Gijsbertus T. J. ;
Cooper, Priscilla K. ;
Hoeijmakers, Jan H. J. ;
van der Pluijm, Ingrid .
PLOS GENETICS, 2014, 10 (10)
[7]
Subconjunctival Injection of XG-102, a JNK Inhibitor Peptide, in Patients with Intraocular Inflammation: A Safety and Tolerability Study [J].
Beydoun, Talal ;
Deloche, Catherine ;
Perino, Julien ;
Kirwan, Bridget-Anne ;
Combette, Jean-Marc ;
Behar-Cohen, Francine .
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 2015, 31 (02) :93-99
[8]
A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia [J].
Borsello, T ;
Clarke, PGH ;
Hirt, L ;
Vercelli, A ;
Repici, M ;
Schorderet, DF ;
Bogousslavsky, J ;
Bonny, C .
NATURE MEDICINE, 2003, 9 (09) :1180-1186
[9]
Early role for IL-6 signalling during generation of induced pluripotent stem cells revealed by heterokaryon RNA-Seq [J].
Brady, Jennifer J. ;
Li, Mavis ;
Suthram, Silpa ;
Jiang, Hui ;
Wong, Wing H. ;
Blau, Helen M. .
NATURE CELL BIOLOGY, 2013, 15 (10) :1244-U272
[10]
Bypass of senescence after disruption of p21(CIP1/WAF1) gene in normal diploid human fibroblasts [J].
Brown, JP ;
Wei, WY ;
Sedivy, JM .
SCIENCE, 1997, 277 (5327) :831-834