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Review
. 2021 Dec:200:111591.
doi: 10.1016/j.mad.2021.111591. Epub 2021 Oct 23.

Strategies for late phase preclinical and early clinical trials of senolytics

Erin O Wissler Gerdes  1 , Avanish Misra  1 , Jair Machado Espindola Netto  1 , Tamar Tchkonia  2 , James L Kirkland  3
Affiliations
Review

Strategies for late phase preclinical and early clinical trials of senolytics

Erin O Wissler Gerdes et al. Mech Ageing Dev. 2021 Dec.

Abstract

Cellular senescence and the hallmarks of aging contribute to age-related disease and dysfunction. The Unitary Theory of Fundamental Aging Mechanisms highlights the interdependence among the hallmarks of aging and suggests that by intervening in one fundamental aging process, most or all of the other processes could be impacted. Accumulation of senescent cells is associated with frailty, cardiovascular disease, obesity, diabetes, cognitive decline, and other age- and/or chronic disease-related disorders, suggesting that senescent cells are a target for intervention. Early preclinical data using senolytics, agents that target senescent cells, show promising results in several aging and disease models. The first in-human trials using the senolytic combination of Dasatinib and Quercetin indicated reduced senescent cell burden in adipose tissue of diabetic kidney disease patients and improved physical function in patients with idiopathic pulmonary fibrosis. Clinical trials with other senolytics, including the flavonoid Fisetin and BCL-xL inhibitors, are underway. These results from preclinical and early clinical trials illustrate the potential of senolytics to alleviate age-related dysfunction and diseases. However, multiple clinical trials across different aging and disease models are desperately needed. Parallel trials across institutions through the Translational Geroscience Network are facilitating testing to determine whether senolytics can be translated into clinical application.

Keywords: Dasatinib; Fisetin; Quercetin; Senolytics; Translational Geroscience Network; Unitary Theory of Fundamental Aging Processes.

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Figures

Figure 1:
Figure 1:
The hallmarks of aging may underpin a variety of age-related diseases and disorders, as well as chronic disease in younger individuals.
Figure 2:
Figure 2:
The Translational Geroscience Network (TGN) has subcommittees to achieve the four aims of the network.
See this image and copyright information in PMC

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