Strategies targeting cellular senescence
Open accessAbstract
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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Inhibitors of the BCL-2 family of anti-apoptotic proteins and peptides inhibiting FOXO4 were identified as senolytics.
“Similar approaches led to the identification of inhibitors of the B-cell lymphoma 2 (BCL-2) family of anti-apoptotic proteins, and peptides inhibiting FOXO4 as senolytics (Ovadya and Krizhanovsky 2018).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Ovadya and Krizhanovsky 2018
Bcl2 family inhibitors are the most widely used senolytics and are effective at killing a range of senescent cells in vivo.
“Currently Bcl2 family inhibitors are the most widely used senolytics, having been shown effective at killing a range of senescent cells in vivo”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [23]
Senescent cells play a causal role in many age-related diseases via expression of the senescence-associated secretory phenotype to secrete inflammatory mediators and proteases.
“They play a causal role in many age-related diseases (such as neurodegenerative and cardiovascular diseases, osteoarthritis, and cancer) via expression of the senescence-associated secretory phenotype (SASP) to secret various inflammatory mediators and proteases1–7.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [5]
Senescent cells accumulate with age and as a result of exposure to a variety of stressors including radiation.
“SCs accumulate with age and as a result of the exposure to a variety of stressors including radiation.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [5]
Different senescent cells can use different anti-apoptotic pathways (SCAPs) to resist apoptosis.
“This observation is in agreement with the suggestion that different SCs can use different anti-apoptotic pathways (SCAPs) to resist apoptosis2–5.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [5]
Senescent cells from different cellular origins and tissues show variable sensitivities to different senolytic agents.
“Our studies also confirm some of the previous observations that SCs from different cellular origins and tissues show variable sensitivities to different senolytic agents2–5.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [5]
Immune cells can remove senescent cells.
“Immune cells can remove senescent cells.”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [121]
Generally, senescent cells can be removed by apoptosis and the immune system.
“Generally, senescent cells can be removed by apoptosis and the immune system [121,122].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [121]
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- Authors
- Ovadya, Y., & Krizhanovsky, V.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Krizhanovsky, Valery
- ORCID
- Krizhanovsky, Valery
- Venue
- Journal of Clinical Investigation
- Published
- 2018-04-02
- Volume
- 128
- Issue
- 4
- Pages
- 1247-1254
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5873866
- OpenAlex
- W2794642028
- Cited by
- 200
- References
- 107
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 26 · 2023: 24 · 2022: 29 · 2021: 24 · 2020: 40 · 2019: 23 · 2018: 10
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (H2020)
- Weizmann Institute of Science
- Israel Science Foundation
- Horizon 2020 Framework Programme
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senolytics, senolytic therapy, senescent cell elimination, age-related diseases, senescence-associated secretory phenotype, aging, carcinogenesis
- MeSH terms
- Aging, Animals, Cell Transformation, Neoplastic, Humans, Immunologic Surveillance, Neoplasms, Cellular Senescence
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