Senolytics: Difference between revisions
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* {{SeeWikipedia|Senolytic}} | * {{SeeWikipedia|Senolytic}} | ||
== Todo == | |||
* 2019: Scientists at the [[Mayo Clinic]] report the first successful use of [[Senolytics|senolytics]], a new class of drug with potential anti-aging benefits, to remove [[Cellular senescence|senescent cells]] from human patients with a kidney disease. | |||
<ref>{{cite web|url=https://newsnetwork.mayoclinic.org/discussion/mayo-researchers-demonstrate-senescent-cell-burden-is-reduced-in-humans-by-senolytic-drugs/|title=Mayo researchers demonstrate senescent cell burden is reduced in humans by senolytic drugs|work=Mayo Clinic|date=18 September 2019|access-date=20 September 2019}}</ref><ref>{{cite web|url=https://www.ebiomedicine.com/article/S2352-3964(19)30591-2/pdf|title=Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease|work=EBioMedicine|date=20 September 2019|access-date=20 September 2019}}</ref> | |||
* 2021: Scientists report alternative approach to [[Senolytics|senolytics]] for removing [[Senescent cells|senescent cells]]: [[Natural killer T cell#Invariant%20NKT%20(iNKT)%20cells|invariant NKT (iNKT) cells]].<ref>{{cite news|title=Scientists find mechanism that eliminates senescent cells|url=https://medicalxpress.com/news/2021-05-scientists-mechanism-senescent-cells.html|access-date=28 June 2021|work=medicalxpress.com|language=en}}</ref><ref>{{cite journal|vauthors=Arora S, Thompson PJ, Wang Y, Bhattacharyya A, Apostolopoulou H, Hatano R, Naikawadi RP, Shah A, Wolters PJ, Koliwad S, Bhattacharya M, Bhushan A|display-authors=6|title=Invariant Natural Killer T cells coordinate removal of senescent cells|language=English|journal=Med|volume=2|issue=8|pages=938–950|date=August 2021|pmid=34617070|pmc=8491998|doi=10.1016/j.medj.2021.04.014|doi-access=free}}</ref> | |||
* 2022: [[Biogerontology|Biomedical gerontologists]] demonstrate a mechanism of anti-aging [[Senolytic|senolytics]], in particular of [[Dasatinib]] plus [[Quercetin]] (D+Q) – an increase [[Klotho (biology)#Effects%20on%20aging|of α-Klotho]] as shown in mice, human cells and in a [[Clinical trial|human trial]].<ref>{{cite news|title=Senolytic drugs boost key protective protein|url=https://newsnetwork.mayoclinic.org/discussion/senolytic-drugs-boost-key-protective-protein/|access-date=19 April 2022|work=Mayo Clinic News Network|date=15 March 2022}}</ref><ref>{{cite journal|vauthors=Zhu Y, Prata LG, Gerdes EO, Netto JM, Pirtskhalava T, Giorgadze N, Tripathi U, Inman CL, Johnson KO, Xue A, Palmer AK, Chen T, Schaefer K, Justice JN, Nambiar AM, Musi N, Kritchevsky SB, Chen J, Khosla S, Jurk D, Schafer MJ, Tchkonia T, Kirkland JL|display-authors=6|title=Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans|language=English|journal=eBioMedicine|volume=77|pages=103912|date=March 2022|pmid=35292270|pmc=9034457|doi=10.1016/j.ebiom.2022.103912}}</ref> | |||
* 2022: Scientists report that some apparently [[Senescent cell|senescent cells]] – which are targeted by anti-aging [[Senolytics|senolytics]] – are required for regeneration, and suggest tailoring senolytics to precisely target harmful senescent cells while leaving the ones involved in regeneration intact.<ref>{{cite news|title=Scientists reappraise the role of 'zombie' cells that anti-aging medicine has sought to eliminate|url=https://medicalxpress.com/news/2022-10-scientists-reappraise-role-zombie-cells.html|access-date=20 November 2022|work=University of San Francisco via medicalxpress.com|language=en}}</ref><ref>{{cite journal|vauthors=Reyes NS, Krasilnikov M, Allen NC, Lee JY, Hyams B, Zhou M, Ravishankar S, Cassandras M, Wang C, Khan I, Matatia P, Johmura Y, Molofsky A, Matthay M, Nakanishi M, Sheppard D, Campisi J, Peng T|display-authors=6|title=Sentinel ''p16''<sup>INK4a+</sup> cells in the basement membrane form a reparative niche in the lung|journal=Science|volume=378|issue=6616|pages=192–201|date=October 2022|pmid=36227993|doi=10.1126/science.abf3326|s2cid=219636762|bibcode=2022Sci...378..192R|biorxiv=10.1101/2020.06.10.142893|pmc=10621323}}</ref> | |||
* 2023: First [[Senolytic|senolytics]] discovered using artificial intelligence:<ref>{{cite web|title=AI helps discover three drugs which could fight effects of ageing|date=14 June 2023|work=Sky News|url=https://news.sky.com/story/ai-helps-discover-three-drugs-which-could-fight-effects-of-ageing-12902182}}</ref><ref>{{cite web|title=AI finds drugs that could kill 'zombie cells' behind ageing|url=https://www.thetimes.co.uk/article/ai-finds-drugs-that-could-kill-zombie-cells-behind-ageing-g6929hstl#:~:text=The%20AI%20selected%2021%20compounds,senescent%20drug%20of%20its%20kind|vauthors=Puttic H|date=15 June 2023|work=The Times}}</ref> Teams from the [[University of Edinburgh]] and the [[Massachusetts Institute of Technology]] independently report the discovery of senolytics using [[Artificial intelligence|artificial intelligence]] for screening large chemical libraries. The works reported compounds of comparable efficacy and increased potency than other known senolytics.<ref>{{cite journal|vauthors=Smer-Barreto V, Quintanilla A, Elliott RJ, Dawson JC, Sun J, Campa VM, Lorente-Macías Á, Unciti-Broceta A, Carragher NO, Acosta JC, Oyarzún DA|display-authors=6|title=Discovery of senolytics using machine learning|journal=Nature Communications|volume=14|issue=1|pages=3445|date=June 2023|pmid=37301862|pmc=10257182|doi=10.1038/s41467-023-39120-1|bibcode=2023NatCo..14.3445S}}</ref><ref>{{cite journal|vauthors=Wong F, Omori S, Donghia NM, Zheng EJ, Collins JJ|title=Discovering small-molecule senolytics with deep neural networks|journal=Nature Aging|pages=734–750|date=May 2023|volume=3|issue=6|pmid=37142829|doi=10.1038/s43587-023-00415-z|s2cid=258506382}}</ref> | |||
== References == | |||
<references /> | |||
[[Category:Senolytic Compounds|!Senolytics]] | [[Category:Senolytic Compounds|!Senolytics]] | ||
Revision as of 09:34, 31 December 2023
Senolytics are compounds designed to target and eliminate senescent cells. Senescent cells are cells that have stopped dividing and have entered a state of permanent growth arrest without undergoing cell death, known as apoptosis. Despite their arrested growth, these cells can affect surrounding tissues through their secretion of inflammatory cytokines, growth factors, and proteases, a phenomenon known as the senescence-associated secretory phenotype (SASP).
Senescent cells accumulate with age and are thought to contribute to various age-related diseases, such as cardiovascular diseases, neurodegenerative disorders, and various types of cancer, by promoting inflammation and tissue dysfunction. By selectively inducing death in senescent cells, senolytics aim to reduce this burden and alleviate age-related ailments, potentially extending healthy lifespan.
Researchers are investigating various compounds as potential senolytics, including naturally occurring compounds like quercetin, fisetin, and more targeted synthetic drugs. The field is relatively new but rapidly growing, with increasing interest in how clearing senescent cells can improve health and combat diseases associated with aging. However, while promising in preclinical studies, the safety and efficacy of senolytic drugs are still being evaluated in clinical trials.
See Also
- Senescent Cells
- Wikipedia - Senolytic
Todo
- 2019: Scientists at the Mayo Clinic report the first successful use of senolytics, a new class of drug with potential anti-aging benefits, to remove senescent cells from human patients with a kidney disease.
- 2021: Scientists report alternative approach to senolytics for removing senescent cells: invariant NKT (iNKT) cells.[3][4]
- 2022: Biomedical gerontologists demonstrate a mechanism of anti-aging senolytics, in particular of Dasatinib plus Quercetin (D+Q) – an increase of α-Klotho as shown in mice, human cells and in a human trial.[5][6]
- 2022: Scientists report that some apparently senescent cells – which are targeted by anti-aging senolytics – are required for regeneration, and suggest tailoring senolytics to precisely target harmful senescent cells while leaving the ones involved in regeneration intact.[7][8]
- 2023: First senolytics discovered using artificial intelligence:[9][10] Teams from the University of Edinburgh and the Massachusetts Institute of Technology independently report the discovery of senolytics using artificial intelligence for screening large chemical libraries. The works reported compounds of comparable efficacy and increased potency than other known senolytics.[11][12]
References
- ↑ Mayo researchers demonstrate senescent cell burden is reduced in humans by senolytic drugs, https://newsnetwork.mayoclinic.org/discussion/mayo-researchers-demonstrate-senescent-cell-burden-is-reduced-in-humans-by-senolytic-drugs/
- ↑ Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease, https://www.ebiomedicine.com/article/S2352-3964(19)30591-2/pdf
- ↑ Template:cite news
- ↑ Arora S, Thompson PJ, Wang Y, Bhattacharyya A, Apostolopoulou H, Hatano R, Naikawadi RP, Shah A, Wolters PJ, Koliwad S, Bhattacharya M, Bhushan A; "Invariant Natural Killer T cells coordinate removal of senescent cells" , https://doi.org/10.1016/j.medj.2021.04.014
- ↑ Template:cite news
- ↑ Zhu Y, Prata LG, Gerdes EO, Netto JM, Pirtskhalava T, Giorgadze N, Tripathi U, Inman CL, Johnson KO, Xue A, Palmer AK, Chen T, Schaefer K, Justice JN, Nambiar AM, Musi N, Kritchevsky SB, Chen J, Khosla S, Jurk D, Schafer MJ, Tchkonia T, Kirkland JL; "Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans" , https://doi.org/10.1016/j.ebiom.2022.103912
- ↑ Template:cite news
- ↑ Reyes NS, Krasilnikov M, Allen NC, Lee JY, Hyams B, Zhou M, Ravishankar S, Cassandras M, Wang C, Khan I, Matatia P, Johmura Y, Molofsky A, Matthay M, Nakanishi M, Sheppard D, Campisi J, Peng T; "Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung" , https://doi.org/10.1126/science.abf3326
- ↑ AI helps discover three drugs which could fight effects of ageing, https://news.sky.com/story/ai-helps-discover-three-drugs-which-could-fight-effects-of-ageing-12902182
- ↑ AI finds drugs that could kill 'zombie cells' behind ageing, https://www.thetimes.co.uk/article/ai-finds-drugs-that-could-kill-zombie-cells-behind-ageing-g6929hstl#:~:text=The%20AI%20selected%2021%20compounds,senescent%20drug%20of%20its%20kind
- ↑ Smer-Barreto V, Quintanilla A, Elliott RJ, Dawson JC, Sun J, Campa VM, Lorente-Macías Á, Unciti-Broceta A, Carragher NO, Acosta JC, Oyarzún DA; "Discovery of senolytics using machine learning" , https://doi.org/10.1038/s41467-023-39120-1
- ↑ Wong F, Omori S, Donghia NM, Zheng EJ, Collins JJ; "Discovering small-molecule senolytics with deep neural networks" , https://doi.org/10.1038/s43587-023-00415-z