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Cellular senescence in renal ageing and disease

Nature Reviews Nephrology volume 13, pages 77–89 (2017)Cite this article

Subjects

Key Points

  • Cellular senescence is a multi-faceted programme involved in diverse physiological and pathological processes including embryonic development, regeneration and repair, cancer-protection, ageing, and disease

  • Senescent cells that are transiently present (acute senescence) are beneficial, whereas prolonged signalling and aberrant accumulation of senescent cells (chronic senescence) impairs renal function and promotes kidney disease

  • Chronic senescent cells accumulate in the kidneys during natural ageing and have been causally linked to age-related decline in renal function

  • Senescent cell accumulation also occurs in association with several renal diseases and therapeutic damage, and correlates with disease progression or deterioration in several instances

  • Therapeutic interventions that target senescent cells, termed senotherapies, have potential to attenuate age-related renal dysfunction, improve disease outcome, and ensure success of kidney transplantation

  • Development of effective and safe senotherapies should greatly benefit from future research aimed at understanding of the location, origin and properties of senescent cells in greater detail

Abstract

The senescence programme is implicated in diverse biological processes, including embryogenesis, tissue regeneration and repair, tumorigenesis, and ageing. Although in vivo studies of senescence are in their infancy, evidence suggesting that senescent cells are a heterogeneous cell type is accumulating: senescence can be induced by different stressors, and senescent cells have varying degrees of genomic and epigenomic instability and different cell origins, contributing to their diversity. Two main classes of senescent cells have been identified: acute and chronic senescent cells. Acute senescent cells are generated during coordinated, beneficial biological processes characterized by a defined senescence trigger, transient senescent-cell signalling functions, and eventual senescent-cell clearance. In contrast, chronic senescent cells arise more slowly from cumulative, diverse stresses and are inefficiently eliminated, leading to their accumulation and deleterious effects through a secretory phenotype. Senescent cells have been identified in many tissues and organs, including the kidney. Here, we discuss the emerging roles of senescent cells in renal development, homeostasis, and pathology. We also address how senotherapy, or targeting of senescent cells, might be used to improve renal function with normal ageing, disease, or therapy-induced damage.

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Figure 1: Main triggers of senescence.
Figure 2: Potential roles of senescent cells during the life of the kidney.
Figure 3: Senescent cell accumulation in the kidney associated with ageing, disease, and therapy.
Figure 4: Senotherapeutic targeting strategies.

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Authors and Affiliations

  1. Departments of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street SW, Rochester, 55905, Minnesota, USA

    Ines Sturmlechner, Matej Durik, Darren J. Baker & Jan M. van Deursen

  2. Department of Pediatrics, Molecular Genetics Section, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands

    Ines Sturmlechner & Jan M. van Deursen

  3. Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, 55905, Minnesota, USA

    Cynthia J. Sieben, Darren J. Baker & Jan M. van Deursen

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All authors researched the data, discussed the article's content, wrote the text and reviewed or edited the article before submission.

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Glossary

Senescence-associated secretory phenotype

(SASP). High amounts of pro-inflammatory and matrix-degrading molecules produced and secreted by senescent cells.

Immune surveillance

Mechanism by which senescent cells are detected and eliminated by the immune system.

Mesonephros

Transitory embryonic excretory organ derived from the metanephric mesenchyme that forms around embryonic day (E) 9 and degenerates by E15.5 in mice.

Functional reserve capacity

Capacity an organ to preserve function, if damage should occur.

Ciliopathies

Group of diseases that arise from mutations in genes encoding primary cilia-related proteins and that affect several organs such as the eyes, limbs and kidneys.

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Sturmlechner, I., Durik, M., Sieben, C. et al. Cellular senescence in renal ageing and disease. Nat Rev Nephrol 13, 77–89 (2017). https://doi.org/10.1038/nrneph.2016.183

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