Strategies targeting cellular senescence - PubMed (original) (raw)

Review

. 2018 Apr 2;128(4):1247-1254.

doi: 10.1172/JCI95149. Epub 2018 Apr 2.

Review

Strategies targeting cellular senescence

Yossi Ovadya et al. J Clin Invest. 2018.

Abstract

Cellular senescence is a physiological phenomenon that has both beneficial and detrimental consequences. Senescence limits tumorigenesis and tissue damage throughout the lifetime. However, at the late stages of life, senescent cells increasingly accumulate in tissues and might also contribute to the development of various age-related pathologies. Recent studies have revealed the molecular pathways that preserve the viability of senescent cells and the ones regulating their immune surveillance. These studies provide essential initial insights for the development of novel therapeutic strategies for targeting senescent cells. At the same time they stress the need to understand the limitations of the existing strategies, their efficacy and safety, and the possible deleterious consequences of senescent cell elimination. Here we discuss the existing strategies for targeting senescent cells and upcoming challenges in translating these strategies into safe and efficient therapies. Successful translation of these strategies could have implications for treating a variety of diseases at old age and could potentially reshape our view of health management during aging.

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Conflict of interest statement

Conflict of interest: YO and VK are inventors on pending patents in the field (PCT/IL2014/050358, PCT/IL2016/050220, and PCT/IL2016/050702 for VK; and PCT/IL2016/050535 for VK and YO).

Figures

Figure 1

Figure 1. Strategies targeting cellular senescence.

Three principal approaches could be implemented to block deleterious effects of senescent cells. (A) The leading options are strategies that induce apoptosis selectively in senescent cells with the use of senolytic drugs, which block prosurvival pathways. (B) The second type of strategy is to potentiate an immune response against senescent cells in a way that would lead to their clearance from tissues. (C) A third strategy proposes specific blockade of SASP components by targeting of their upstream regulators and effectors. ADCC, antibody-dependent cell-mediated cytotoxicity; DDR, DNA damage response; GOS, galacto-oligosaccharides; ITAM, immunoreceptor tyrosine-based activation motif.

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References

    1. World Health Organization. World Report on Ageing And Health. Geneva, Switzerland: World Health Organization; 2015. http://www.who.int/ageing/events/world-report-2015-launch/en/ Accessed February 15, 2018.
    1. Bloom DE, Boersch-Supan A, McGee P, Seike A. Population aging: facts, challenges, and responses. Program on the Global Demography of Aging. No. 71. Harvard University Website. https://cdn1.sph.harvard.edu/wp-content/uploads/sites/1288/2013/10/PGDA_... Accessed February 15, 2018.
    1. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–1217. doi: 10.1016/j.cell.2013.05.039. - DOI - PMC - PubMed
    1. Newgard CB, Sharpless NE. Coming of age: molecular drivers of aging and therapeutic opportunities. J Clin Invest. 2013;123(3):946–950. doi: 10.1172/JCI68833. - DOI - PMC - PubMed
    1. Di Leonardo A, Linke SP, Clarkin K, Wahl GM. DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev. 1994;8(21):2540–2551. doi: 10.1101/gad.8.21.2540. - DOI - PubMed

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