Editing Life extension (section)

===Senolytics and prolongevity drugs===
{{See also|Geroprotector|MTOR inhibitors#Rapamycin and rapalogs}}
{{Excerpt|Senolytic|paragraphs=|file=}}

Senolytics eliminate senescent cells whereas [[senomorphic]]s – with candidates such as [[Apigenin]], [[Everolimus]]<!--(RAD001 in ref)--> and [[Rapamycin]] – modulate properties of senescent cells without eliminating them, suppressing phenotypes of senescence, including the [[Senescence-associated secretory phenotype|SASP]].<ref name="Di Micco-2021">{{cite journal | vauthors = Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F | title = Cellular senescence in ageing: from mechanisms to therapeutic opportunities | journal = Nature Reviews. Molecular Cell Biology | volume = 22 | issue = 2 | pages = 75–95 | date = February 2021 | pmid = 33328614 | pmc = 8344376 | doi = 10.1038/s41580-020-00314-w }}</ref><ref name="Robbins-2021">{{cite journal | vauthors = Robbins PD, Jurk D, Khosla S, Kirkland JL, LeBrasseur NK, Miller JD, Passos JF, Pignolo RJ, Tchkonia T, Niedernhofer LJ | display-authors = 6 | title = Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span | journal = Annual Review of Pharmacology and Toxicology | volume = 61 | issue = 1 | pages = 779–803 | date = January 2021 | pmid = 32997601 | pmc = 7790861 | doi = 10.1146/annurev-pharmtox-050120-105018 }}</ref> Senomorphic effects may be one major effect mechanism of a range of prolongevity drug candidates. Such candidates are however typically not studied for just one mechanism, but multiple. There are [[biological database]]s of prolongevity drug candidates under research as well as of potential gene/protein targets. These are enhanced by longitudinal [[cohort study|cohort studies]], [[electronic health records]], [[In silico medicine|computational]] (drug) screening methods, computational biomarker-discovery methods and computational biodata-interpretation/[[personalized medicine]] methods.<ref name="Donertas-2019">{{cite journal | vauthors = Dönertaş HM, Fuentealba M, Partridge L, Thornton JM | title = Identifying Potential Ageing-Modulating Drugs In Silico | journal = Trends in Endocrinology and Metabolism | volume = 30 | issue = 2 | pages = 118–131 | date = February 2019 | pmid = 30581056 | pmc = 6362144 | doi = 10.1016/j.tem.2018.11.005 }}</ref><ref name="Zhavoronkov-2019"/><ref name="Partridge-2018">{{cite journal | vauthors = Partridge L, Deelen J, Slagboom PE | title = Facing up to the global challenges of ageing | journal = Nature | volume = 561 | issue = 7721 | pages = 45–56 | date = September 2018 | pmid = 30185958 | doi = 10.1038/s41586-018-0457-8 | bibcode = 2018Natur.561...45P | s2cid = 52161707 | hdl = 1887/75460 | hdl-access = free }}</ref>

Besides rapamycin and senolytics, the [[Drug repositioning|drug-repurposing]] candidates studied most extensively include [[metformin]], [[acarbose]], [[spermidine]] and [[Nicotinamide adenine dinucleotide|NAD+]] enhancers.<ref>{{cite journal | vauthors = Partridge L, Fuentealba M, Kennedy BK | title = The quest to slow ageing through drug discovery | journal = Nature Reviews. Drug Discovery | volume = 19 | issue = 8 | pages = 513–532 | date = August 2020 | pmid = 32467649 | doi = 10.1038/s41573-020-0067-7 | s2cid = 218912510 | url = https://discovery.ucl.ac.uk/id/eprint/10101648/ }}</ref>

Many prolongevity drugs are synthetic alternatives or potential complements to existing nutraceuticals, such as various [[sirtuin-activating compound]]s under investigation like [[SRT2104]].<ref>{{cite journal | vauthors = Bonkowski MS, Sinclair DA | title = Slowing ageing by design: the rise of NAD<sup>+</sup> and sirtuin-activating compounds | journal = Nature Reviews. Molecular Cell Biology | volume = 17 | issue = 11 | pages = 679–690 | date = November 2016 | pmid = 27552971 | pmc = 5107309 | doi = 10.1038/nrm.2016.93 }}</ref> {{anchor|GlyNAC}}In some cases pharmaceutical administration is combined with that of neutraceuticals – such as in the case of [[glycine]] combined with [[N-acetylcysteine|NAC]].<ref name="Sekhar-2021">{{cite journal | vauthors = Sekhar RV | title = GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging | journal = The Journal of Nutrition | volume = 151 | issue = 12 | pages = 3606–3616 | date = December 2021 | pmid = 34587244 | doi = 10.1093/jn/nxab309 | doi-access = free }}</ref> Often studies are structured based on or thematize specific prolongevity targets, listing both nutraceuticals and pharmaceuticals (together or separately) such as [[FOXO3]]-activators.<ref>{{cite journal | vauthors = McIntyre RL, Liu YJ, Hu M, Morris BJ, Willcox BJ, Donlon TA, Houtkooper RH, Janssens GE | display-authors = 6 | title = Pharmaceutical and nutraceutical activation of FOXO3 for healthy longevity | journal = Ageing Research Reviews | volume = 78 | pages = 101621 | date = June 2022 | pmid = 35421606 | doi = 10.1016/j.arr.2022.101621 | s2cid = 248089515 | doi-access = free }}</ref>

Researchers are also exploring ways to mitigate side-effects from such substances (possibly most notably [[MTOR inhibitors#Rapamycin and rapalogs|rapamycin and its derivatives]]) such as via protocols of intermittent administration<ref>{{cite journal | vauthors = Kirkland JL, Tchkonia T | title = Senolytic drugs: from discovery to translation | journal = Journal of Internal Medicine | volume = 288 | issue = 5 | pages = 518–536 | date = November 2020 | pmid = 32686219 | pmc = 7405395 | doi = 10.1111/joim.13141 }}</ref><ref name="Robbins-2021"/><ref name="Di Micco-2021"/><ref>{{cite journal | vauthors = Palmer AK, Gustafson B, Kirkland JL, Smith U | title = Cellular senescence: at the nexus between ageing and diabetes | journal = Diabetologia | volume = 62 | issue = 10 | pages = 1835–1841 | date = October 2019 | pmid = 31451866 | pmc = 6731336 | doi = 10.1007/s00125-019-4934-x }}</ref><ref>{{cite journal | vauthors = Blagosklonny MV | title = Fasting and rapamycin: diabetes versus benevolent glucose intolerance | journal = Cell Death & Disease | volume = 10 | issue = 8 | pages = 607 | date = August 2019 | pmid = 31406105 | pmc = 6690951 | doi = 10.1038/s41419-019-1822-8 }}</ref> and have called for research that helps determine optimal [[treatment schedules]] (including timing) in general.<ref>{{cite journal | vauthors = Martel J, Chang SH, Wu CY, Peng HH, Hwang TL, Ko YF, Young JD, Ojcius DM | display-authors = 6 | title = Recent advances in the field of caloric restriction mimetics and anti-aging molecules | journal = Ageing Research Reviews | volume = 66 | pages = 101240 | date = March 2021 | pmid = 33347992 | doi = 10.1016/j.arr.2020.101240 | s2cid = 229351578 }}</ref>