Senescent cells as new pharmacological targets for age-related diseases and anti-aging therapy

Authors

  • Michal M. Masternak University of Central Florida College of Medicine, Burnett School of Biomedical Sciences, Orlando, FL, USA; Department of Head and Neck Surgery, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0002-8483-930X

DOI:

https://doi.org/10.20883/medical.e907

Keywords:

aging, senescence, senolytics

Abstract

Aging is a natural process leading to decline in physical function, reducing ability to adjust to everyday organismal stress and increased frailty. Recent studies of the mechanism of aging have brought attention to naturally occurring senescent cells in different organs throughout the body. This natural process of senescence is caused by cell cycle arrest due to cellular damage, which protects cells from apoptosis, while stimulating the production and secretion of different senescent associated secretory phenotypes (SASPs) causing low grade chronic inflammation. Emerging studies show that by targeting and eliminating these cells with a new class of senolytic drugs in old animals we can improve a variety of health conditions including reduction of inflammation, improvement of insulin sensitivity and metabolic status, increase of bone mineral density and enhanced physical function together with extended overall longevity. Ongoing clinical trials using Desatanib and Quarcetin (D+Q) and other classes of senolytic drugs indicate high translational potentials in targeting and clearing senescent cells to cure some age-related diseases; however, more in depth studies have to be completed to incorporate these therapies in general healthy elderly populations for safe anti-aging intervention.

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References

Danczak-Pazdrowska, A., et al., Cellular senescence in skin-related research: Targeted signaling pathways and naturally occurring therapeutic agents. Aging Cell, 2023. 22(6): p. e13845.

Xu, M., et al., Senolytics improve physical function and increase lifespan in old age. Nat Med, 2018. 24(8): p. 1246-1256.

Cavalcante, M.B., et al., Dasatinib plus quercetin prevents uterine age-related dysfunction and fibrosis in mice. Aging (Albany NY), 2020. 12(3): p. 2711-2722.

Saccon, T.D., et al., Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice. J Gerontol A Biol Sci Med Sci, 2021. 76(11): p. 1895-1905.

Nunes, A.D.C., et al., miR-146a-5p modulates cellular senescence and apoptosis in visceral adipose tissue of long-lived Ames dwarf mice and in cultured pre-adipocytes. Geroscience, 2022. 44(1): p. 503-518.

Noureddine, S., et al., microRNA-449a reduces growth hormone-stimulated senescent cell burden through PI3K-mTOR signaling. Proc Natl Acad Sci U S A, 2023. 120(14): p. e2213207120.

Justice, J.N., et al., Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 2019. 40: p. 554-563.

Hense, J.D., et al., Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary. Geroscience, 2022. 44(3): p. 1747-1759.

Nambiar, A., et al., Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability. EBioMedicine, 2023. 90: p. 104481.

Robbins, P.D., et al., Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span. Annu Rev Pharmacol Toxicol, 2021. 61: p. 779-803.

Zhu, Y., et al., Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell, 2016. 15(3): p. 428-35.

Roos, C.M., et al., Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 2016. 15(5): p. 973-7.

Farr, J.N., et al., Targeting cellular senescence prevents age-related bone loss in mice. Nat Med, 2017. 23(9): p. 1072-1079.

Palmer, A.K., et al., Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell, 2019. 18(3): p. e12950.

Riordan, R., et al., Effect of Nrf2 loss on senescence and cognition of tau-based P301S mice. Geroscience, 2023.

Dorigatti, A.O., et al., Brain cellular senescence in mouse models of Alzheimer's disease. Geroscience, 2022. 44(2): p. 1157-1168.

Hickson, L.J., et al., Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 2019. 47: p. 446-456.

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Published

2023-09-29

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How to Cite

1.
Masternak MM. Senescent cells as new pharmacological targets for age-related diseases and anti-aging therapy. JMS [Internet]. 2023 Sep. 29 [cited 2024 Dec. 26];92(3):e907. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/907