Senotherapeutics for healthy ageing
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Senolytics, small molecules that selectively kill senescent cells, have the potential to prevent and treat various age-related diseases and extend healthspan.
“Small molecules that can selectively kill SCs, termed senolytics, have the potential to prevent and treat a growing number of age-related diseases and extend healthspan2–4.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [4]
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 [4]
Almost all targeted senolytics are repurposed anticancer agents except the FOXO4-p53 interfering peptide.
“By contrast, almost all the targeted senolytics are repurposed anticancer agents except the FOXO4-p53 interfering peptide2–4.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [4]
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 [4]
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 [4]
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 [4]
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Fisetin is a senotherapeutic that extends health and lifespan
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Self-citationEmerging senolytic agents derived from natural products
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“While the search for successful senolytic drugs continues, combination therapies that include senolytics and senomorphics have been suggested; it is possible that DPP4 inhibitors could be used in a similar manner (71).”
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A dual-enzyme activated fluorescent probe for precise identification of tumor senescence
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Epigenetic dysregulation in cardiovascular aging and disease
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The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs
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- Authors
- Niedernhofer, L. J., & Robbins, P. D.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Niedernhofer, Laura J.
- Robbins, Paul D.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2018-04-13
- Volume
- 17
- Issue
- 5
- Pages
- 377-377
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2797460879
- Cited by
- 190
- References
- 10
- Citations by year
- 2026: 19 · 2025: 15 · 2024: 26 · 2023: 44 · 2022: 28 · 2021: 25 · 2020: 13 · 2019: 14 · 2018: 6
- FWCI
- 9.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Glenn Foundation for Medical Research
- National Institutes of Health (AG043376, AG056278)
- National Institute on Aging (P01AG043376, R01AG044376)
- 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, healthy aging, fisetin, Bcl-xL inhibitors, Hsp90 inhibitors, NF-κB inhibition, JAK inhibition, senescence-associated secretory phenotype, frailty, p16INK4a, senolytic therapy, post-traumatic osteoarthritis
- MeSH terms
- Healthy Aging, Aging, Cellular Senescence
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