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Is cellular senescence important in pediatric kidney disease?

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Abstract

Somatic cellular senescence (SCS) describes the limited ability of cells to divide. Normally, SCS is associated with physiological aging, but evidence suggests that it may play a role in disease progression, even in young patients. Stressors such as acute injury or chronic inflammation may induce SCS, which in turn exhausts organ regenerative potential. This review summarizes what is known about SCS in the kidney with aging and disease. As most patients with chronic kidney disease (CKD) also develop cardiovascular complications, a second focus of this review deals with the role of SCS in cardiovascular disease. Also, as SCS seems to accelerate CKD and cardiovascular disease progression, developing strategies for new treatment options that overcome SCS or protect a patient from it represents an exciting challenge.

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Abbreviations

ACE:

angiotensin-converting enzyme

ANRIL:

antisense noncoding RNA in the INK4 locus

ApoE:

apolipoprotein E

ARF:

alternate open reading frame

ATM:

ataxia telangiectasia mutated

ATR:

ataxia telangiectasia mutated and Rad3-related

CIP1:

cyclin-dependent kinase-interacting protein 1

CKD:

chronic kidney disease

CRP:

C-reactive protein

eNOS:

endothelial nitric oxide synthase

HDM2:

human double minute 2

HUS:

hemolytic uremic syndrome

INK4:

inhibitor of cyclin-dependent kinase 4

KIP:

cyclin-dependent kinase-inhibitory protein

MAPK:

mitogen-activated protein kinase

MDM2:

mouse double minute 2

mTOR:

mammalian target of rapamycin

NO:

nitric oxide

PBMC:

peripheral blood mononuclear cell

PIKK:

phosphatidylinositol 3 kinase-like kinases

Rb:

retinoblastoma protein

S6K1:

ribosomal protein s6 kinase 1

SA-β-GAL:

senescence-associated-β-galactosidase

SCS:

somatic cellular senescence

SNP:

single nucleotide polymorphism

SOD2:

partial mitochondrial superoxide dismutase

STASIS:

stimulation and stress-induced senescence-like arrest

WAF1:

wild-type p53-activated fragment 1

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Acknowledgements

The authors thank C. Martin-Ruiz for providing the image of RT-PCR in Fig. 1. The images of Telomere Q-FISH were adapted by permission from Macmillan Publishers Ltd: Nature Protocols [103]. We thank Nathan Susnik for critically reading and improving the manuscript.

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  1. Department of Pediatric Nephrology, Gastroenterology and Metabolic Diseases, Children’s Hospital, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Christoph Jacobi, Meike Hömme & Anette Melk

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  1. Christoph Jacobi
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  2. Meike Hömme
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  3. Anette Melk
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Correspondence to Anette Melk.

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Jacobi, C., Hömme, M. & Melk, A. Is cellular senescence important in pediatric kidney disease?. Pediatr Nephrol 26, 2121–2131 (2011). https://doi.org/10.1007/s00467-010-1740-6

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  • DOI: https://doi.org/10.1007/s00467-010-1740-6

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