Editing Life extension (section)

==Beliefs and methods==
{{See also|Ageing#Prevention and delay|Brain aging}}

===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>

===Diets and supplements===
====Vitamins and antioxidants====
{{See also|Inflammaging|DNA damage theory of aging}}
The [[free-radical theory of aging]] suggests that [[antioxidant]] supplements might extend human life. Reviews, however, have found that use of vitamin A (as β-carotene) and vitamin E supplements possibly can increase mortality.<ref>{{cite journal | vauthors = Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C | title = Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis | journal = JAMA | volume = 297 | issue = 8 | pages = 842–857 | date = February 2007 | pmid = 17327526 | doi = 10.1001/jama.297.8.842 }}</ref><ref>{{cite journal | vauthors = Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C | title = Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 3 | pages = CD007176 | date = March 2012 | pmid = 22419320 | pmc = 8407395 | doi = 10.1002/14651858.CD007176.pub2 | hdl-access = free | hdl = 10138/136201 }}</ref> Other reviews have found no relationship between vitamin E and other vitamins with mortality.<ref>{{cite journal | vauthors = Jiang S, Pan Z, Li H, Li F, Song Y, Qiu Y | title = Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality | journal = Journal of Nutritional Science and Vitaminology | volume = 60 | issue = 3 | pages = 194–205 | year = 2014 | pmid = 25078376 | doi = 10.3177/jnsv.60.194 | quote = Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality. | doi-access = free }}</ref> [[Vitamin D]] supplementation of various dosages is investigated in trials<ref>{{cite journal | vauthors = Garay RP | title = Investigational drugs and nutrients for human longevity. Recent clinical trials registered in ClinicalTrials.gov and clinicaltrialsregister.eu | journal = Expert Opinion on Investigational Drugs | volume = 30 | issue = 7 | pages = 749–758 | date = July 2021 | pmid = 34081543 | doi = 10.1080/13543784.2021.1939306 | s2cid = 235334397 }}</ref> and there also is research into GlyNAC {{see above|[[#GlyNAC|above]]}}.<ref name="Sekhar-2021"/>

====Complications====
Complications of antioxidant supplementation (especially continuous high dosages far above the [[Recommended Daily Allowance|RDA]]) include that [[reactive oxygen species]] (ROS), which are mitigated by antioxidants, "have been found to be physiologically vital for signal transduction, gene regulation, and redox regulation, among others, implying that their complete elimination would be harmful". In particular, one way of multiple they can be detrimental is by inhibiting adaptation to exercise such as [[muscle hypertrophy]] (e.g. during [[bodybuilding|dedicated periods]] of caloric surplus).<ref>{{cite journal | vauthors = Damiano S, Muscariello E, La Rosa G, Di Maro M, Mondola P, Santillo M | title = Dual Role of Reactive Oxygen Species in Muscle Function: Can Antioxidant Dietary Supplements Counteract Age-Related Sarcopenia? | journal = International Journal of Molecular Sciences | volume = 20 | issue = 15 | pages = E3815 | date = August 2019 | pmid = 31387214 | pmc = 6696113 | doi = 10.3390/ijms20153815 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Badran A, Nasser SA, Mesmar J, El-Yazbi AF, Bitto A, Fardoun MM, Baydoun E, Eid AH | display-authors = 6 | title = Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells | journal = International Journal of Molecular Sciences | volume = 21 | issue = 22 | pages = 8764 | date = November 2020 | pmid = 33233489 | doi = 10.3390/ijms21228764 | pmc = 7699590 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sohal RS, Orr WC | title = The redox stress hypothesis of aging | journal = Free Radical Biology & Medicine | volume = 52 | issue = 3 | pages = 539–555 | date = February 2012 | pmid = 22080087 | pmc = 3267846 | doi = 10.1016/j.freeradbiomed.2011.10.445 }}</ref> There is also research into stimulating/activating/fueling endogenous antioxidant generation, in particular e.g. of neutraceutical glycine and pharmaceutical NAC.<ref>{{cite journal | vauthors = McCarty MF, O'Keefe JH, DiNicolantonio JJ | title = Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection | journal = The Ochsner Journal | volume = 18 | issue = 1 | pages = 81–87 | date = 2018 | pmid = 29559876 | pmc = 5855430 }}</ref> Antioxidants can change the oxidation status of different e.g. tissues, targets or sites each with potentially different implications, especially for different concentrations.<ref>{{cite journal | vauthors = Griffiths HR | title = Antioxidants and protein oxidation | journal = Free Radical Research | volume = 33 | issue = Supplement | pages = S47–S58 | date = November 2000 | pmid = 11191275 | url = https://publications.aston.ac.uk/id/eprint/39762/ }}</ref><ref>{{cite journal | vauthors = Cobley JN | title = Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing | journal = Antioxidants | volume = 9 | issue = 10 | pages = 933 | date = September 2020 | pmid = 33003362 | pmc = 7599503 | doi = 10.3390/antiox9100933 | doi-access = free }}</ref><ref>{{cite journal | title = Nutritional Antioxidants: It Is Time to Categorise | journal = Antioxidants in Sport Nutrition | date = 2015 | pmid = 26065087 | url = https://pubmed.ncbi.nlm.nih.gov/26065087/ | publisher = CRC Press/Taylor & Francis | isbn = 9781466567573 | last1 = Bast | first1 = A. | author2 = Haenen GRMM | last3 = Lamprecht | first3 = M. }}</ref><ref>{{cite journal |last1=Lobo |first1=V |last2=Patil |first2=A |last3=Phatak |first3=A |last4=Chandra |first4=N |date=2010 |title=Free radicals, antioxidants and functional foods: Impact on human health |journal=Pharmacognosy Reviews |volume=4 |issue=8 |pages=118–126 |doi=10.4103/0973-7847.70902 |pmid=22228951 |pmc=3249911 |doi-access=free }}</ref> A review suggests [[mitochondria]] have a [[hormesis|hormetic]] response to ROS, whereby low oxidative damage can be beneficial.<ref>{{cite journal | vauthors = Hood WR, Zhang Y, Mowry AV, Hyatt HW, Kavazis AN | title = Life History Trade-offs within the Context of Mitochondrial Hormesis | journal = Integrative and Comparative Biology | volume = 58 | issue = 3 | pages = 567–577 | date = September 2018 | pmid = 30011013 | pmc = 6145418 | doi = 10.1093/icb/icy073 }}</ref>

====Dietary restriction====
{{main|Diet and longevity}}
{{See also|Caloric restriction mimetic}}
As of 2021, there is no [[evidence-based medicine|clinical evidence]] that any dietary restriction practice contributes to human longevity.<ref>{{cite journal |vauthors=Lee MB, Hill CM, Bitto A, Kaeberlein M |date=November 2021 |title=Antiaging diets: Separating fact from fiction |journal=Science |volume=374 |issue=6570 |pages=eabe7365 |doi=10.1126/science.abe7365 |pmc=8841109 |pmid=34793210}}</ref>

====Healthy diet====
Research suggests that increasing adherence to [[Mediterranean diet]] patterns is associated with a reduction in total and cause-specific mortality, extending health- and lifespan.<ref>{{cite journal | vauthors = Dominguez LJ, Di Bella G, Veronese N, Barbagallo M | title = Impact of Mediterranean Diet on Chronic Non-Communicable Diseases and Longevity | journal = Nutrients | volume = 13 | issue = 6 | pages = 2028 | date = June 2021 | pmid = 34204683 | doi = 10.3390/nu13062028 | pmc = 8231595 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Eleftheriou D, Benetou V, Trichopoulou A, La Vecchia C, Bamia C | title = Mediterranean diet and its components in relation to all-cause mortality: meta-analysis | journal = The British Journal of Nutrition | volume = 120 | issue = 10 | pages = 1081–1097 | date = November 2018 | pmid = 30401007 | doi = 10.1017/S0007114518002593 | s2cid = 53226475 | doi-access = free | hdl = 2434/612956 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Ekmekcioglu C | title = Nutrition and longevity - From mechanisms to uncertainties | journal = Critical Reviews in Food Science and Nutrition | volume = 60 | issue = 18 | pages = 3063–3082 | date = 2020 | pmid = 31631676 | doi = 10.1080/10408398.2019.1676698 | s2cid = 204815279 }}</ref><ref name="niha"/> Research is identifying the key beneficial components of the Mediterranean diet.<ref>{{cite journal | vauthors = Hidalgo-Mora JJ, García-Vigara A, Sánchez-Sánchez ML, García-Pérez MÁ, Tarín J, Cano A | title = The Mediterranean diet: A historical perspective on food for health | language = English | journal = Maturitas | volume = 132 | pages = 65–69 | date = February 2020 | pmid = 31883665 | doi = 10.1016/j.maturitas.2019.12.002 | s2cid = 209510802 }}</ref><ref>{{cite journal | vauthors = Vasto S, Barera A, Rizzo C, Di Carlo M, Caruso C, Panotopoulos G | title = Mediterranean diet and longevity: an example of nutraceuticals? | journal = Current Vascular Pharmacology | volume = 12 | issue = 5 | pages = 735–738 | date = 2014 | pmid = 24350926 | doi = 10.2174/1570161111666131219111818 }}</ref> Studies suggest dietary changes are a factor of [[List of countries by life expectancy|national]] relative rises in life-span.<ref>{{cite journal | vauthors = Tsugane S | title = Why has Japan become the world's most long-lived country: insights from a food and nutrition perspective | journal = European Journal of Clinical Nutrition | volume = 75 | issue = 6 | pages = 921–928 | date = June 2021 | pmid = 32661353 | pmc = 8189904 | doi = 10.1038/s41430-020-0677-5 }}</ref>

====Optimal diet====
{{See also|Sustainable consumption#Sustainable food consumption}}
Approaches to develop optimal diets for health- and lifespan (or "longevity diets")<ref name="Longo-2022"/> include:
* modifying the Mediterranean diet as the baseline via [[nutrition science]]. For instance, via:
**(additional) increase in [[plant-based diet|plant-based]]<ref>{{cite journal | vauthors = Mariotti F, Gardner CD | title = Dietary Protein and Amino Acids in Vegetarian Diets-A Review | journal = Nutrients | volume = 11 | issue = 11 | pages = 2661 | date = November 2019 | pmid = 31690027 | pmc = 6893534 | doi = 10.3390/nu11112661 | doi-access = free }}</ref><ref name="Longo-2022"/> foods alongside additional restriction of [[Meat#Health|meat intake]]<ref>{{cite journal | vauthors = Fong BY, Chiu WK, Chan WF, Lam TY | title = A Review Study of a Green Diet and Healthy Ageing | journal = International Journal of Environmental Research and Public Health | volume = 18 | issue = 15 | pages = 8024 | date = July 2021 | pmid = 34360317 | doi = 10.3390/ijerph18158024 | pmc = 8345706 | doi-access = free }}</ref> – [[Environmental impact of meat production#Meat reduction and health|meat reduction is (or can be) typically healthy]],<ref>{{cite journal | vauthors = Parlasca MC, Qaim M |title=Meat Consumption and Sustainability |journal=Annual Review of Resource Economics |date=5 October 2022 |volume=14 |issue=1 |pages=17–41 |doi=10.1146/annurev-resource-111820-032340 |issn=1941-1340|doi-access=free }}</ref>
**keeping alcohol consumption of any type at a minimum – conventional Mediterranean diets include alcohol consumption (i.e. [[Health effects of wine#Moderate consumption|of wine]]), which is under research due to [[long-term impact of alcohol on the brain|data suggesting negative long-term brain impacts]] even at low/moderate consumption levels.<ref>{{cite journal | title = Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 | journal = Lancet | volume = 392 | issue = 10152 | pages = 1015–1035 | date = September 2018 | pmid = 30146330 | pmc = 6148333 | doi = 10.1016/S0140-6736(18)31310-2 | last1 = Griswold | first1 = Max G. | last2 = Fullman | first2 = Nancy | last3 = Hawley | first3 = Caitlin | last4 = Arian | first4 = Nicholas | last5 = Zimsen | first5 = Stephanie R M. | last6 = Tymeson | first6 = Hayley D. | last7 = Venkateswaran | first7 = Vidhya | last8 = Tapp | first8 = Austin Douglas | last9 = Forouzanfar | first9 = Mohammad H. | last10 = Salama | first10 = Joseph S. | last11 = Abate | first11 = Kalkidan Hassen | last12 = Abate | first12 = Degu | last13 = Abay | first13 = Solomon M. | last14 = Abbafati | first14 = Cristiana | last15 = Abdulkader | first15 = Rizwan Suliankatchi | last16 = Abebe | first16 = Zegeye | last17 = Aboyans | first17 = Victor | last18 = Abrar | first18 = Mohammed Mehdi | last19 = Acharya | first19 = Pawan | last20 = Adetokunboh | first20 = Olatunji O. | last21 = Adhikari | first21 = Tara Ballav | last22 = Adsuar | first22 = Jose C. | last23 = Afarideh | first23 = Mohsen | last24 = Agardh | first24 = Emilie Elisabet | last25 = Agarwal | first25 = Gina | last26 = Aghayan | first26 = Sargis Aghasi | last27 = Agrawal | first27 = Sutapa | last28 = Ahmed | first28 = Muktar Beshir | last29 = Akibu | first29 = Mohammed | last30 = Akinyemiju | first30 = Tomi | display-authors = 1 }}</ref><ref>{{cite web |title=Facts about moderate drinking {{!}} CDC |url=https://www.cdc.gov/alcohol/fact-sheets/moderate-drinking.htm |website=www.cdc.gov |language=en-us |date=19 April 2022}}</ref> 
**fully replacing refined grains – some guidelines of Mediterranean diets do not clarify or include the principle of [[whole-grain]] consumption instead of refined grains. Whole grains are included in Mediterranean diets.<ref>{{cite journal | vauthors = Widmer RJ, Flammer AJ, Lerman LO, Lerman A | title = The Mediterranean diet, its components, and cardiovascular disease | journal = The American Journal of Medicine | volume = 128 | issue = 3 | pages = 229–238 | date = March 2015 | pmid = 25447615 | pmc = 4339461 | doi = 10.1016/j.amjmed.2014.10.014 }}</ref><ref>{{cite journal | vauthors = Ventriglio A, Sancassiani F, Contu MP, Latorre M, Di Slavatore M, Fornaro M, Bhugra D | title = Mediterranean Diet and its Benefits on Health and Mental Health: A Literature Review | journal = Clinical Practice and Epidemiology in Mental Health | volume = 16 | issue = Suppl-1 | pages = 156–164 | date = 2020 | pmid = 33029192 | pmc = 7536728 | doi = 10.2174/1745017902016010156 }}</ref>

===Other approaches===
Further advanced biosciences-based approaches include:
* '''Genetic and epigenetic alterations''': [[Human genetic enhancement]] for pro-longevity and protective genes – see [[genetics of aging]]<ref>{{cite journal | vauthors = Delhove J, Osenk I, Prichard I, Donnelley M | title = Public Acceptability of Gene Therapy and Gene Editing for Human Use: A Systematic Review | journal = Human Gene Therapy | volume = 31 | issue = 1–2 | pages = 20–46 | date = January 2020 | pmid = 31802714 | doi = 10.1089/hum.2019.197 | s2cid = 208645665 }}</ref><ref name="Zhavoronkov-2019"/>
* '''Cellular reprogramming''': in vivo [[Induced pluripotent stem cell|reprogramming]] to complement or augment [[Regeneration in humans|human regenerative capacity]] and rejuvenate or replace cells<ref>{{cite journal | vauthors = Beyret E, Martinez Redondo P, Platero Luengo A, Izpisua Belmonte JC | title = Elixir of Life: Thwarting Aging With Regenerative Reprogramming | journal = Circulation Research | volume = 122 | issue = 1 | pages = 128–141 | date = January 2018 | pmid = 29301845 | pmc = 5823281 | doi = 10.1161/CIRCRESAHA.117.311866 }}</ref><ref>{{cite journal | vauthors = Yener Ilce B, Cagin U, Yilmazer A | title = Cellular reprogramming: A new way to understand aging mechanisms | journal = Wiley Interdisciplinary Reviews. Developmental Biology | volume = 7 | issue = 2 | date = March 2018 | pmid = 29350802 | doi = 10.1002/wdev.308 | s2cid = 46743444 }}</ref><ref name="Zhavoronkov-2019"/>
* '''Epigenetic reprogramming''': early-stage research about rejuvenating/repairing [[epigenetic]] machinery<ref>{{cite journal | vauthors = Topart C, Werner E, Arimondo PB | title = Wandering along the epigenetic timeline | journal = Clinical Epigenetics | volume = 12 | issue = 1 | pages = 97 | date = July 2020 | pmid = 32616071 | pmc = 7330981 | doi = 10.1186/s13148-020-00893-7 | doi-access = free }}</ref>
* '''Stem-cell interventions''': "Increasing the number and quality of stem cells and activate regenerative signals"<ref name="Ullah-2018"/><ref>{{cite journal |last1=Baraniak |first1=Priya R |last2=McDevitt |first2=Todd C |title=Stem cell paracrine actions and tissue regeneration |journal=Regenerative Medicine |date=January 2010 |volume=5 |issue=1 |pages=121–143 |doi=10.2217/rme.09.74 |pmid=20017699 |pmc=2833273 }}</ref>
* '''[[Nanobiotechnology#Nanomedicine|Nanomedicine]]''': early-stage research of in vivo pro-longevity nanotechnology<ref>{{cite journal | vauthors = Rzigalinski BA, Meehan K, Davis RM, Xu Y, Miles WC, Cohen CA | title = Radical nanomedicine | journal = Nanomedicine | volume = 1 | issue = 4 | pages = 399–412 | date = December 2006 | pmid = 17716143 | doi = 10.2217/17435889.1.4.399 }}</ref><ref>{{cite journal |last1=Ventola |first1=CL |title=The nanomedicine revolution: part 2: current and future clinical applications. |journal=P & T: A Peer-Reviewed Journal for Formulary Management |date=October 2012 |volume=37 |issue=10 |pages=582–91 |pmid=23115468 |pmc=3474440 }}</ref>
* '''[[Tissue engineering]]''': of tissues and organs<ref>{{cite journal | vauthors = Khorraminejad-Shirazi M, Dorvash M, Estedlal A, Hoveidaei AH, Mazloomrezaei M, Mosaddeghi P | title = Aging: A cell source limiting factor in tissue engineering | journal = World Journal of Stem Cells | volume = 11 | issue = 10 | pages = 787–802 | date = October 2019 | pmid = 31692986 | doi = 10.4252/wjsc.v11.i10.787 | pmc = 6828594 | s2cid = 207894219 | doi-access = free }}</ref> (see also: [[xenotransplantation]] and [[artificial organ]])
*{{anchor|EndogenousCirculatingBiomolecules}}'''Endogenous circulating biomolecules''': [[Blood protein]]s of blood from young animals have shown some pro-longevity potential in animal studies (e.g. via transfer of blood or plasma, and of plasma proteins).<ref name="Partridge-2018"/> Moreover, [[exerkine]]s – signalling biomolecules released during/after exercise – have also shown promising results.<ref name="Chow-2022">{{cite journal | vauthors = Chow LS, Gerszten RE, Taylor JM, Pedersen BK, van Praag H, Trappe S, Febbraio MA, Galis ZS, Gao Y, Haus JM, Lanza IR, Lavie CJ, Lee CH, Lucia A, Moro C, Pandey A, Robbins JM, Stanford KI, Thackray AE, Villeda S, Watt MJ, Xia A, Zierath JR, Goodpaster BH, Snyder MP | display-authors = 6 | title = Exerkines in health, resilience and disease | journal = Nature Reviews. Endocrinology | volume = 18 | issue = 5 | pages = 273–289 | date = May 2022 | pmid = 35304603 | doi = 10.1038/s41574-022-00641-2 | pmc = 9554896 | s2cid = 247524287 }}</ref> Exerkines include [[myokine]]s. [[Extracellular vesicles]] were shown to be secreted concomitantly with exerkines and are also investigated.<ref>{{cite journal | vauthors = Nederveen JP, Warnier G, Di Carlo A, Nilsson MI, Tarnopolsky MA | title = Extracellular Vesicles and Exosomes: Insights From Exercise Science | journal = Frontiers in Physiology | volume = 11 | pages = 604274 | date = 2020 | pmid = 33597890 | pmc = 7882633 | doi = 10.3389/fphys.2020.604274 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lananna BV, Imai SI | title = Friends and foes: Extracellular vesicles in aging and rejuvenation | journal = FASEB BioAdvances | volume = 3 | issue = 10 | pages = 787–801 | date = October 2021 | pmid = 34632314 | pmc = 8493967 | doi = 10.1096/fba.2021-00077 | doi-access = free }}</ref> (See also: [[body fluid]] and [[cerebrospinal fluid]])
*{{anchor|PersonalizedInterventions}}'''Personalized interventions''': future studies may tailor and investigate [[personalized medicine]]-type interventions.<ref name="Campisi-2019">{{cite journal | vauthors = Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E | title = From discoveries in ageing research to therapeutics for healthy ageing | journal = Nature | volume = 571 | issue = 7764 | pages = 183–192 | date = July 2019 | pmid = 31292558 | pmc = 7205183 | doi = 10.1038/s41586-019-1365-2 | bibcode = 2019Natur.571..183C }}</ref> For instance, effects of interventions or e.g. dosages may vary per age<ref name="Longo-2022"/> and/or genome. A review suggests that the field of [[precision medicine]] and geroscience will have to interact closely<ref name="Campisi-2019"/> (see also: [[combination therapy]])
* '''Peptides''': such as [[MT-RNR1|MOTS-c]] released by mitochondria<ref name="Lopez-Otin-2016">{{cite journal | vauthors = López-Otín C, Galluzzi L, Freije JM, Madeo F, Kroemer G | title = Metabolic Control of Longevity | journal = Cell | volume = 166 | issue = 4 | pages = 802–821 | date = August 2016 | pmid = 27518560 | doi = 10.1016/j.cell.2016.07.031 | s2cid = 2316555 | doi-access = free }}</ref>
* '''Mitochondria modulation''': early-stage research indicates mitochondrial interventions such as mitochondrial transplantation may have potential to be efficacious<ref>{{cite journal | vauthors = Tomita K, Kuwahara Y, Igarashi K, Roudkenar MH, Roushandeh AM, Kurimasa A, Sato T | title = Mitochondrial Dysfunction in Diseases, Longevity, and Treatment Resistance: Tuning Mitochondria Function as a Therapeutic Strategy | journal = Genes | volume = 12 | issue = 9 | pages = 1348 | date = August 2021 | pmid = 34573330 | doi = 10.3390/genes12091348 | pmc = 8467098 | doi-access = free }}</ref><ref name="Zhavoronkov-2019"/><ref>{{cite journal | vauthors = Akbari M, Kirkwood TB, Bohr VA | title = Mitochondria in the signaling pathways that control longevity and health span | journal = Ageing Research Reviews | volume = 54 | pages = 100940 | date = September 2019 | pmid = 31415807 | pmc = 7479635 | doi = 10.1016/j.arr.2019.100940 }}</ref><ref>{{cite journal | vauthors = Akbari M, Kirkwood TB, Bohr VA | title = Mitochondria in the signaling pathways that control longevity and health span | journal = Ageing Research Reviews | volume = 54 | pages = 100940 | date = September 2019 | pmid = 31415807 | doi = 10.1016/j.arr.2019.100940 | pmc = 7479635 | s2cid = 199544098 }}</ref><ref>{{cite journal | vauthors = Santoro A, Martucci M, Conte M, Capri M, Franceschi C, Salvioli S | title = Inflammaging, hormesis and the rationale for anti-aging strategies | journal = Ageing Research Reviews | volume = 64 | pages = 101142 | date = December 2020 | pmid = 32814129 | doi = 10.1016/j.arr.2020.101142 | s2cid = 221136388 }}</ref> (See also: [[mitochondrial theory of ageing]])

====Within the field====
{{See also|Biogerontology}}
There is a need and research into the development of aging [[biomarker]]s such as the [[epigenetic clock]] "to assess the ageing process and the efficacy of interventions to bypass the need for large-scale longitudinal studies".<ref name="Campisi-2019"/><ref name="Zhavoronkov-2019">{{cite journal | vauthors = Zhavoronkov A, Mamoshina P, Vanhaelen Q, Scheibye-Knudsen M, Moskalev A, Aliper A | title = Artificial intelligence for aging and longevity research: Recent advances and perspectives | journal = Ageing Research Reviews | volume = 49 | pages = 49–66 | date = January 2019 | pmid = 30472217 | doi = 10.1016/j.arr.2018.11.003 | s2cid = 53755842 | doi-access = free }}</ref> Such biomarkers may also include in vivo [[brain imaging]].<ref>{{cite journal | vauthors = Ingram DK, Chefer S, Matochik J, Moscrip TD, Weed J, Roth GS, London ED, Lane MA | display-authors = 6 | title = Aging and caloric restriction in nonhuman primates: behavioral and in vivo brain imaging studies | journal = Annals of the New York Academy of Sciences | volume = 928 | pages = 316–326 | date = April 2001 | issue = 1 | pmid = 11795523 | doi = 10.1111/j.1749-6632.2001.tb05661.x | s2cid = 35478202 }}</ref>

Reviews sometimes include structured tables that provide systematic overviews of intervention/drug candidates with a review calling for integrating "current knowledge with multi-omics, health records, and drug safety data to predict drugs that can improve health in late life" and listing [[research question|major outstanding questions]].<ref name="Donertas-2019"/> [[Biological database]]s of prolongevity drug candidates under research as well as of potential gene/protein targets include GenAge, DrugAge and Geroprotectors.<ref name="Donertas-2019"/><ref>{{cite journal | vauthors = Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, Ortolano S, Pani G, Athanasopoulou S, Gonos ES, Schosserer M, Grillari J, Peterson P, Tuna BG, Dogan S, Meyer A, van Os R, Trendelenburg AU | display-authors = 6 | title = Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases | journal = Ageing Research Reviews | volume = 47 | pages = 214–277 | date = November 2018 | pmid = 30071357 | doi = 10.1016/j.arr.2018.07.004 | s2cid = 51865989 | doi-access = free | hdl = 10807/130553 | hdl-access = free }}</ref>

A review has pointed out that the approach of "'epidemiological' comparison of how a low versus a high consumption of an isolated macronutrient and its association with health and mortality may not only fail to identify protective or detrimental nutrition patterns but may lead to misleading interpretations". It proposes a multi-pillar approach, and summarizes findings towards constructing – multi-system-considering and at least age-personalized dynamic – refined longevity diets. Epidemiological-type observational studies included in meta-analyses should according to the study at least be complemented by "(1) basic research focused on lifespan and healthspan, (2) carefully controlled clinical trials, and (3) studies of individuals and populations with record longevity".<ref name="Longo-2022">{{cite journal | vauthors = Longo VD, Anderson RM | title = Nutrition, longevity and disease: From molecular mechanisms to interventions | language = English | journal = Cell | volume = 185 | issue = 9 | pages = 1455–1470 | date = April 2022 | pmid = 35487190 | pmc = 9089818 | doi = 10.1016/j.cell.2022.04.002 }}</ref>

===Hormone treatment===
The [[anti-aging]] industry offers several [[hormone therapies]]. Some of these have been criticized for possible dangers and a lack of proven effect. For example, the [[American Medical Association]] has been critical of some anti-aging hormone therapies.<ref name=AMA>{{Cite news | vauthors = Japsen B |date=15 June 2009 |title=AMA report questions science behind using hormones as anti-aging treatment |url=https://www.chicagotribune.com/2009/06/15/anti-aging-treatment-on-amas-radar/ |work=[[The Chicago Tribune]] |access-date=17 July 2009}}</ref>

While [[growth hormone]] (GH) decreases with age, the evidence for use of growth hormone as an anti-aging therapy is mixed and based mostly on animal studies. There are mixed reports that GH or [[IGF-1]] modulates the aging process in humans and about whether the direction of its effect is positive or negative.<ref>{{cite journal | vauthors = Sattler FR | title = Growth hormone in the aging male | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 27 | issue = 4 | pages = 541–555 | date = August 2013 | pmid = 24054930 | pmc = 3940699 | doi = 10.1016/j.beem.2013.05.003 | quote = In animal models, alterations in GH/IGF-1 signaling with reductions in these somatotrophs appear to increase life span. &nbsp;... Administration of IGF-1Eb (mechanogrowth factor) stimulates proliferation of myoblasts and induces muscle hypertrophy. Increases in GH and IGF-1 during adolescence are beneficial for brain and cardiovascular function during the aging process and GH administration during adolescence is vasoprotective and increases life-span.<sup>15</sup>&nbsp;... Studies relating GH and IGF-1 status to longevity provide inconsistent evidence as to whether decreased (somatopause) or high levels (e.g. acromegaly) of these hormones are beneficial or detrimental to longevity.&nbsp;... It is difficult to reconcile the largely protective effects of GH/IGF-1 deficiency on longevity in animals with the inconsistent or deleterious effects of low levels or declining GH/IGF-1 during human aging. }}</ref>

[[Klotho (biology)#Effects on aging|Klotho]]<ref name="Ullah-2018">{{cite journal | vauthors = Ullah M, Sun Z | title = Stem cells and anti-aging genes: double-edged sword-do the same job of life extension | journal = Stem Cell Research & Therapy | volume = 9 | issue = 1 | pages = 3 | date = January 2018 | pmid = 29321045 | pmc = 5763529 | doi = 10.1186/s13287-017-0746-4 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Baranowska B, Kochanowski J | title = The metabolic, neuroprotective cardioprotective and antitumor effects of the Klotho protein | journal = Neuro Endocrinology Letters | volume = 41 | issue = 2 | pages = 69–75 | date = September 2020 | pmid = 33185993 | url = https://pubmed.ncbi.nlm.nih.gov/33185993/ }}</ref> and exerkines<ref name="Chow-2022"/> {{See above|[[#EndogenousCirculatingBiomolecules|above]]}} like [[irisin]]<ref>{{cite journal | vauthors = Fossati C, Papalia R, Torre G, Vadalà G, Borrione P, Grazioli E, Mazzola C, Parisi A, Pigozzi F, Denaro V | display-authors = 6 | title = Frailty of the elderly in orthopaedic surgery and body composition changes: the musculoskeletal crosstalk through irisin | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 34 | issue = 4 Suppl. 3 | pages = 327–335. Congress of the Italian Orthopaedic Research Society | date = July 2020 | pmid = 33261297 }}</ref> are being investigated for potential pro-longevity therapies.

===Lifestyle factors===
{{See also|Lifestyle disease}}
[[Loneliness]]/isolation, social life and support,<ref name="niha"/><ref>{{cite journal | vauthors = Vila J | title = Social Support and Longevity: Meta-Analysis-Based Evidence and Psychobiological Mechanisms | journal = Frontiers in Psychology | volume = 12 | pages = 717164 | date = 2021 | pmid = 34589025 | pmc = 8473615 | doi = 10.3389/fpsyg.2021.717164 | doi-access = free }}</ref> exercise/physical activity (partly via [[neurobiological effects of physical exercise|neurobiological effects]] and increased NAD+ levels),<ref name="niha">{{cite web |title=What Do We Know About Healthy Aging? |date=23 February 2022 |url=https://www.nia.nih.gov/health/what-do-we-know-about-healthy-aging |publisher=[[National Institute on Aging]] |access-date=1 June 2022 |language=en}}</ref><ref>{{cite journal | vauthors = O'Keefe EL, Torres-Acosta N, O'Keefe JH, Lavie CJ | title = Training for Longevity: The Reverse J-Curve for Exercise | journal = Missouri Medicine | volume = 117 | issue = 4 | pages = 355–361 | date = July 2020 | pmid = 32848273 | pmc = 7431070 | quote = Current studies suggest that 2.5 to 5 hours/week of moderate or vigorous physical activity will confer maximal benefits; >10 hours/week may reduce these health benefits. }}</ref><ref name="Campisi-2019"/><ref name="Lopez-Otin-2016"/><ref>{{cite journal | vauthors = Min S, Masanovic B, Bu T, Matic RM, Vasiljevic I, Vukotic M, Li J, Vukovic J, Fu T, Jabucanin B, Bujkovic R, Popovic S | display-authors = 6 | title = The Association Between Regular Physical Exercise, Sleep Patterns, Fasting, and Autophagy for Healthy Longevity and Well-Being: A Narrative Review | journal = Frontiers in Psychology | volume = 12 | pages = 803421 | date = 2 December 2021 | pmid = 34925198 | pmc = 8674197 | doi = 10.3389/fpsyg.2021.803421 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F | title = Caloric Restriction Mimetics in Nutrition and Clinical Trials | journal = Frontiers in Nutrition | volume = 8 | pages = 717343 | date = 2021 | pmid = 34552954 | doi = 10.3389/fnut.2021.717343 | pmc = 8450594 | doi-access = free }}</ref> psychological characteristics/personality (possibly highly indirectly),<ref>{{cite journal | vauthors = Chapman BP, Roberts B, Duberstein P | title = Personality and longevity: knowns, unknowns, and implications for public health and personalized medicine | journal = Journal of Aging Research | volume = 2011 | pages = 759170 | date = 10 July 2011 | pmid = 21766032 | doi = 10.4061/2011/759170 | pmc = 3134197 | s2cid = 16615606 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kern ML, Friedman HS | title = Do conscientious individuals live longer? A quantitative review | journal = Health Psychology | volume = 27 | issue = 5 | pages = 505–512 | date = September 2008 | pmid = 18823176 | doi = 10.1037/0278-6133.27.5.505 }}</ref> sleep duration,<ref name="niha"/> [[circadian rhythm]]s (patterns of sleep, drug-administration and feeding),<ref>{{cite journal | vauthors = Froy O, Miskin R | title = Effect of feeding regimens on circadian rhythms: implications for aging and longevity | journal = Aging | volume = 2 | issue = 1 | pages = 7–27 | date = December 2010 | pmid = 20228939 | pmc = 2837202 | doi = 10.18632/aging.100116 }}</ref><ref>{{cite journal | vauthors = Froy O | title = Circadian rhythms, aging, and life span in mammals | journal = Physiology | volume = 26 | issue = 4 | pages = 225–235 | date = August 2011 | pmid = 21841071 | doi = 10.1152/physiol.00012.2011 }}</ref><ref>{{cite journal | vauthors = Acosta-Rodríguez VA, Rijo-Ferreira F, Green CB, Takahashi JS | title = Importance of circadian timing for aging and longevity | journal = Nature Communications | volume = 12 | issue = 1 | pages = 2862 | date = May 2021 | pmid = 34001884 | doi = 10.1038/s41467-021-22922-6 | pmc = 8129076 | bibcode = 2021NatCo..12.2862A | s2cid = 234770669 }}</ref> type of leisure activities,<ref name="niha"/> not smoking,<ref name="niha"/> altruistic emotions and behaviors,<ref>{{cite journal | vauthors = Post SG | title = Altuism, happiness, and health: it's good to be good | journal = International Journal of Behavioral Medicine | volume = 12 | issue = 2 | pages = 66–77 | date = 2005 | pmid = 15901215 | doi = 10.1207/s15327558ijbm1202_4 | s2cid = 12544814 }}</ref><ref>{{cite journal | vauthors = Gottlieb BH, Gillespie AA | title = Volunteerism, health, and civic engagement among older adults | journal = Canadian Journal on Aging | volume = 27 | issue = 4 | pages = 399–406 | date = 2008 | pmid = 19416800 | doi = 10.3138/cja.27.4.399 | s2cid = 24698644 }}</ref> subjective [[well-being]],<ref>{{cite journal | vauthors = Diener E, Oishi S, Tay L | title = Advances in subjective well-being research | journal = Nature Human Behaviour | volume = 2 | issue = 4 | pages = 253–260 | date = April 2018 | pmid = 30936533 | doi = 10.1038/s41562-018-0307-6 | s2cid = 4726262 }}</ref> mood<ref name="niha"/> and stress (including via [[heat shock protein]])<ref name="niha"/><ref>{{cite journal | vauthors = Gomez CR | title = Role of heat shock proteins in aging and chronic inflammatory diseases | journal = GeroScience | volume = 43 | issue = 5 | pages = 2515–2532 | date = October 2021 | pmid = 34241808 | pmc = 8599533 | doi = 10.1007/s11357-021-00394-2 }}</ref> are investigated as potential (modulatable) factors of life extension.

Healthy lifestyle practices and healthy diet have been suggested as "first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential complementary approaches".<ref>{{cite journal | vauthors = Seals DR, Justice JN, LaRocca TJ | title = Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity | journal = The Journal of Physiology | volume = 594 | issue = 8 | pages = 2001–2024 | date = April 2016 | pmid = 25639909 | doi = 10.1113/jphysiol.2014.282665 | pmc = 4933122 | s2cid = 9776021 }}</ref>

===Societal strategies===
{{See also|#Ethics and politics|#Scientific research|Clinical trial|Metascience|Telehealth|Health economics|Health education|Medical research}}
[[File:Life expectancy vs healthcare spending.jpg|thumb|Life expectancy vs healthcare spending of rich OECD countries. [[List of countries by total health expenditure per capita|US average of $10,447 in 2018]].<ref>{{cite journal |author-link1=Max Roser |vauthors=Roser M |date=26 May 2017 |title=Link between health spending and life expectancy: US is an outlier |url=https://ourworldindata.org/the-link-between-life-expectancy-and-health-spending-us-focus |journal=[[Our World in Data]]}} Click the sources tab under the chart for info on the countries, healthcare expenditures, and data sources. See the later version of the chart [https://ourworldindata.org/us-life-expectancy-low here].</ref>]]
Collectively, addressing [[List of causes of death by rate|common causes of death]] could extend lifespans of populations and humanity overall. For instance, a 2020 study indicates that the global mean [[loss of life expectancy]] (LLE) from [[air pollution]] in 2015 was 2.9 years, substantially more than, for example, 0.3 years from all forms of direct violence, albeit a significant fraction of the LLE (a measure similar to [[years of potential life lost]]) is considered to be unavoidable.<ref>{{cite journal | vauthors = Lelieveld J, Pozzer A, Pöschl U, Fnais M, Haines A, Münzel T | title = Loss of life expectancy from air pollution compared to other risk factors: a worldwide perspective | journal = Cardiovascular Research | volume = 116 | issue = 11 | pages = 1910–1917 | date = September 2020 | pmid = 32123898 | pmc = 7449554 | doi = 10.1093/cvr/cvaa025 }}</ref>

Regular [[Screening (medicine)|screening]] and doctor visits has been suggested as a lifestyle-societal intervention.<ref name="niha"/> (See also: [[medical test]] and [[biomarker (medicine)|biomarker]])

[[Health policy]] and changes to standard healthcare could support the adoption of the field's conclusions – a review suggests that the longevity diet would be a "valuable complement to standard healthcare and that, taken as a preventative measure, it could aid in avoiding morbidity, sustaining health into advanced age" as a form of [[preventive healthcare]].<ref name="Longo-2022"/>

It has been suggested that in terms of healthy diets, Mediterranean-style diets could be promoted by countries for ensuring healthy-by-default choices ("to ensure the healthiest choice is the easiest choice") and with highly effective measures including [[Nutrition education|dietary education]], food [[checklist]]s and [[recipe]]s that are "simple, palatable, and affordable".<ref>{{cite journal | vauthors = Murphy KJ, Parletta N | title = Implementing a Mediterranean-Style Diet Outside the Mediterranean Region | journal = Current Atherosclerosis Reports | volume = 20 | issue = 6 | pages = 28 | date = May 2018 | pmid = 29728772 | doi = 10.1007/s11883-018-0732-z | s2cid = 21658334 }}</ref>

A review suggests that "targeting the aging process per se may be a far more effective approach to prevent or delay aging-associated pathologies than treatments specifically targeted to particular clinical conditions".<ref>{{cite journal | vauthors = Vaiserman A, Lushchak O | title = Implementation of longevity-promoting supplements and medications in public health practice: achievements, challenges and future perspectives | journal = Journal of Translational Medicine | volume = 15 | issue = 1 | pages = 160 | date = July 2017 | pmid = 28728596 | pmc = 5520340 | doi = 10.1186/s12967-017-1259-8 | doi-access = free }}</ref>

===Low ambient temperature===
Low ambient temperature as a physical factor affecting free radical levels was identified as a treatment producing exceptional lifespan increase in Drosophila melanogaster and other living beings.<ref>{{cite journal | vauthors = Shaposhnikov MV, Guvatova ZG, Zemskaya NV, Koval LA, Schegoleva EV, Gorbunova AA, Golubev DA, Pakshina NR, Ulyasheva NS, Solovev IA, Bobrovskikh MA, Gruntenko NE, Menshanov PN, Krasnov GS, Kudryavseva AV, Moskalev AA | display-authors = 6 | title = Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions | journal = Communications Biology | volume = 5 | issue = 1 | pages = 566 | date = June 2022 | pmid = 35681084 | pmc = 9184560 | doi = 10.1038/s42003-022-03524-4 }}</ref>
===Young blood conspiracy theory===
{{Further|Young blood transfusion}}
{{Further|blood libel}}
Conspiracy theorists claim that some clinics currently offer injection of blood products from young donors. The alleged benefits of the treatment, none of which have been demonstrated in a proper study, include a longer life, darker hair, better memory, better sleep, curing heart diseases, diabetes and Alzheimer's disease.<ref name=MIT>{{Cite web|url=https://www.technologyreview.com/s/603242/questionable-young-blood-transfusions-offered-in-us-as-anti-aging-remedy/|title=Questionable "Young Blood" Transfusions Offered in U.S. as Anti-Aging Remedy| vauthors = Maxmen A |date=January 13, 2017|website=MIT Technology Review|access-date=November 5, 2017}}</ref><ref name=natpost>{{Cite news|url=https://nationalpost.com/news/world/why-a-silicon-valley-company-is-pumping-old-people-full-of-young-blood-for-us8000|title=This anti-aging startup says US$8,000 worth of young blood can help you live longer| vauthors = Kirkey S |date=November 2, 2017|work=National Post|access-date=November 5, 2017}}</ref><ref name=indep>{{Cite news|url=https://www.independent.co.uk/news/science/teenagers-blood-transfusion-ambrosia-san-francisco-jesse-karmazin-a7902916.html |archive-url=https://ghostarchive.org/archive/20220614/https://www.independent.co.uk/news/science/teenagers-blood-transfusion-ambrosia-san-francisco-jesse-karmazin-a7902916.html |archive-date=2022-06-14 |url-access=subscription |url-status=live|title=Teenagers' blood being sold for £6,200 a shot| vauthors = Osborne S |date=August 20, 2017|work=The Independent}}</ref><ref>{{Cite news|url=https://www.theguardian.com/society/shortcuts/2017/aug/21/ambrosia-the-startup-harvesting-the-blood-of-the-young|title=Ambrosia: the startup harvesting the blood of the young| vauthors = Haynes G |date=August 21, 2017|newspaper=The Guardian|access-date=November 5, 2017}}</ref><ref>{{Cite news|url=https://www.cnbc.com/2017/05/31/blood-transfusions-from-teenagers-start-up-charging-8000-apiece.html|title=This start-up is offering $8,000 blood transfusions from teens to people who want to fight aging| vauthors = Farr C |date=May 31, 2017|work=CNBC|access-date=November 5, 2017}}</ref> The approach is based on [[parabiosis]] studies such as those Irina Conboy has done on mice, but Conboy says young blood does not reverse aging (even in mice) and that those who offer those treatments have misunderstood her research.<ref name=natpost/><ref name=indep/> Neuroscientist Tony Wyss-Coray, who also studied blood exchanges on mice as recently as 2014, said people offering those treatments are "basically abusing people's trust"<ref name=vanfair/><ref name=indep/> and that young blood treatments are "the scientific equivalent of fake news".<ref name=quartz>{{Cite news|url=https://qz.com/996190/ambrosia-says-a-transfusion-of-young-blood-plasma-lowered-disease-markers-in-a-human-trial/|title=A startup that charges $8,000 for young blood transfusions swears they're worth every penny| vauthors = Foley KE |date=June 1, 2017|work=Quartz|access-date=November 5, 2017}}</ref> The treatment appeared in HBO's ''[[Silicon Valley (TV series)|Silicon Valley]]'' fiction series.<ref name=vanfair>{{Cite magazine|url=https://www.vanityfair.com/news/2017/06/this-anti-aging-start-up-is-paying-thousands-of-dollars-for-teen-blood|title=This anti-aging start-up is charging thousands of dollars for teen blood| vauthors = Kosoff M |date=June 1, 2017|magazine=Vanity Fair|access-date=November 5, 2017}}</ref>

Two clinics in California, run by Jesse Karmazin and David C. Wright,<ref name=MIT/> offer $8,000 injections of plasma extracted from the blood of young people. Karmazin has not published in any peer-reviewed journal and his current study does not use a control group.<ref name=quartz/><ref name=vanfair/><ref name=MIT/><ref name=indep/>

===Microbiome alterations===
[[Fecal microbiota transplant]]ation<ref>{{cite news | vauthors = Haridy R |title=Gut bacteria from young mice reverse signs of brain aging in old mice |url=https://newatlas.com/science/microbiome-brain-aging-gut-bacteria-neuroscience/ |access-date=21 September 2021 |work=New Atlas |date=10 August 2021}}</ref><ref>{{cite journal | vauthors = Boehme M, Guzzetta KE, Bastiaanssen TF, Van De Wouw M, Moloney GM, Gual-Grau A, Spichak S, Olavarría-Ramírez L, Fitzgerald P, Morillas E, Ritz NL, Jaggar M, Cowan CS, Crispie F, Donoso F, Halitzki E, Neto MC, Sichetti M, Golubeva AV, Fitzgerald RS, Claesson MJ, Cotter PD, O'Leary OF, Dinan TG, Cryan JF | display-authors = 6 |title=Microbiota from young mice counteracts selective age-associated behavioral deficits |journal=Nature Aging |date=August 2021 |volume=1 |issue=8 |pages=666–676 |doi=10.1038/s43587-021-00093-9 | pmid = 37117767 |language=en |issn=2662-8465|doi-access=free }}</ref> and [[probiotics]] are being investigated as means for life and healthspan extension.<ref>{{cite journal | vauthors = Sharma D, Kober MM, Bowe WP | title = Anti-Aging Effects of Probiotics | journal = Journal of Drugs in Dermatology | volume = 15 | issue = 1 | pages = 9–12 | date = January 2016 | pmid = 26741377 | url = https://pubmed.ncbi.nlm.nih.gov/26741377/ }}</ref><ref>{{cite journal | vauthors = Ayala FR, Bauman C, Cogliati S, Leñini C, Bartolini M, Grau R | title = Microbial flora, probiotics, ''Bacillus subtilis'' and the search for a long and healthy human longevity | journal = Microbial Cell | volume = 4 | issue = 4 | pages = 133–136 | date = March 2017 | pmid = 28435840 | pmc = 5376353 | doi = 10.15698/mic2017.04.569 }}</ref><ref>{{cite journal | vauthors = Tsai YC, Cheng LH, Liu YW, Jeng OJ, Lee YK | title = Gerobiotics: probiotics targeting fundamental aging processes | journal = Bioscience of Microbiota, Food and Health | volume = 40 | issue = 1 | pages = 1–11 | date = 2021 | pmid = 33520563 | pmc = 7817508 | doi = 10.12938/bmfh.2020-026 }}</ref>