The Clinical Potential of Senolytic Drugs

James L Kirkland, Tamara Tchkonia, Yi Zhu, Laura J. Niedernhofer, Paul D. Robbins

Research output: Contribution to journalArticle

  • 30 Citations

Abstract

Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage. Senolytic agents are being tested in proof-of-concept clinical trials. To do so, new clinical trial paradigms for testing senolytics and other agents that target fundamental aging mechanisms are being developed, because use of long-term endpoints such as lifespan or healthspan is not feasible. These strategies include testing effects on multimorbidity, accelerated aging-like conditions, diseases with localized accumulation of senescent cells, potentially fatal diseases associated with senescent cell accumulation, age-related loss of physiological resilience, and frailty. If senolytics or other interventions that target fundamental aging processes prove to be effective and safe in clinical trials, they could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.

LanguageEnglish (US)
JournalJournal of the American Geriatrics Society
DOIs
StateAccepted/In press - 2017

Fingerprint

Pharmaceutical Preparations
Clinical Trials
Geriatrics
Vascular Calcification
Intervertebral Disc Degeneration
Pulmonary Fibrosis
Fatty Liver
Osteoporosis
Comorbidity
Diabetes Mellitus
Chronic Disease
Medicine
Pharmacology
Radiation
Apoptosis
Pathology
Phenotype
Therapeutics
Multiple Chronic Conditions

Keywords

  • Cellular senescence
  • Chronic diseases
  • Geroscience hypothesis
  • SCAPs
  • Senolytics

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J., & Robbins, P. D. (Accepted/In press). The Clinical Potential of Senolytic Drugs. Journal of the American Geriatrics Society. https://doi.org/10.1111/jgs.14969

The Clinical Potential of Senolytic Drugs. / Kirkland, James L; Tchkonia, Tamara; Zhu, Yi; Niedernhofer, Laura J.; Robbins, Paul D.

In: Journal of the American Geriatrics Society, 2017.

Research output: Contribution to journalArticle

Kirkland, James L ; Tchkonia, Tamara ; Zhu, Yi ; Niedernhofer, Laura J. ; Robbins, Paul D. / The Clinical Potential of Senolytic Drugs. In: Journal of the American Geriatrics Society. 2017.
@article{30e9b380ffb44a6f858be775a8d06eff,
title = "The Clinical Potential of Senolytic Drugs",
abstract = "Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage. Senolytic agents are being tested in proof-of-concept clinical trials. To do so, new clinical trial paradigms for testing senolytics and other agents that target fundamental aging mechanisms are being developed, because use of long-term endpoints such as lifespan or healthspan is not feasible. These strategies include testing effects on multimorbidity, accelerated aging-like conditions, diseases with localized accumulation of senescent cells, potentially fatal diseases associated with senescent cell accumulation, age-related loss of physiological resilience, and frailty. If senolytics or other interventions that target fundamental aging processes prove to be effective and safe in clinical trials, they could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.",
keywords = "Cellular senescence, Chronic diseases, Geroscience hypothesis, SCAPs, Senolytics",
author = "Kirkland, {James L} and Tamara Tchkonia and Yi Zhu and Niedernhofer, {Laura J.} and Robbins, {Paul D.}",
year = "2017",
doi = "10.1111/jgs.14969",
language = "English (US)",
journal = "Journal of the American Geriatrics Society",
issn = "0002-8614",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - The Clinical Potential of Senolytic Drugs

AU - Kirkland, James L

AU - Tchkonia, Tamara

AU - Zhu, Yi

AU - Niedernhofer, Laura J.

AU - Robbins, Paul D.

PY - 2017

Y1 - 2017

N2 - Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage. Senolytic agents are being tested in proof-of-concept clinical trials. To do so, new clinical trial paradigms for testing senolytics and other agents that target fundamental aging mechanisms are being developed, because use of long-term endpoints such as lifespan or healthspan is not feasible. These strategies include testing effects on multimorbidity, accelerated aging-like conditions, diseases with localized accumulation of senescent cells, potentially fatal diseases associated with senescent cell accumulation, age-related loss of physiological resilience, and frailty. If senolytics or other interventions that target fundamental aging processes prove to be effective and safe in clinical trials, they could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.

AB - Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage. Senolytic agents are being tested in proof-of-concept clinical trials. To do so, new clinical trial paradigms for testing senolytics and other agents that target fundamental aging mechanisms are being developed, because use of long-term endpoints such as lifespan or healthspan is not feasible. These strategies include testing effects on multimorbidity, accelerated aging-like conditions, diseases with localized accumulation of senescent cells, potentially fatal diseases associated with senescent cell accumulation, age-related loss of physiological resilience, and frailty. If senolytics or other interventions that target fundamental aging processes prove to be effective and safe in clinical trials, they could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.

KW - Cellular senescence

KW - Chronic diseases

KW - Geroscience hypothesis

KW - SCAPs

KW - Senolytics

UR - http://www.scopus.com/inward/record.url?scp=85028699170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028699170&partnerID=8YFLogxK

U2 - 10.1111/jgs.14969

DO - 10.1111/jgs.14969

M3 - Article

JO - Journal of the American Geriatrics Society

T2 - Journal of the American Geriatrics Society

JF - Journal of the American Geriatrics Society

SN - 0002-8614

ER -