Resveratrol - Revision history

Dmitry Dzhagarov: /* Derivatives of resveratrol and drug development attempts */

2024-08-07T18:16:28Z

Derivatives of resveratrol and drug development attempts

← Older revision		Revision as of 18:16, 7 August 2024
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	== Derivatives of resveratrol and drug development attempts ==		== Derivatives of resveratrol and drug development attempts ==
	In 2004 a company called Sirtris Pharmaceuticals, Inc. was conceived to study potential of resveratrol as a drug for type 2 diabetes, cancer, and other diseases. The company's initial product was called SRT501, and was a formulation of reservatrol. In 2008 Sirtris was purchased by the pharma giant GlaxoSmithKline (GSK).<ref>http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html</ref> Further development of SRT501 were terminated in 2010, in part due to its side effects and lack of specificity to SIRT1, followed by shutdown of Sirtis in 2013. <ref>Popat, R., Plesner, T., Davies, F., Cook, G., Cook, M., Elliott, P., ... & Cavenagh, J. (2012). A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. ''British journal of haematology'', ''160''(5), 714-717. https://doi.org/10.1111/bjh.12154 </ref>		In 2004 a company called Sirtris Pharmaceuticals, Inc. was conceived to study potential of resveratrol as a drug for type 2 diabetes, cancer, and other diseases. The company's initial product was called SRT501, and was a formulation of reservatrol. In 2008 Sirtris was purchased by the pharma giant GlaxoSmithKline (GSK).<ref>http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html</ref> Further development of SRT501 were terminated in 2010, in part due to its side effects and lack of specificity to SIRT1, followed by shutdown of Sirtis in 2013. <ref>Popat, R., Plesner, T., Davies, F., Cook, G., Cook, M., Elliott, P., ... & Cavenagh, J. (2012). A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. ''British journal of haematology'', ''160''(5), 714-717. https://doi.org/10.1111/bjh.12154 </ref>

			== Resveratrol Discussion - Is It Really Good For You? ==
			Since ancient times, red wine has been prescribed by all doctors as a means of strengthening the body and promoting longevity. Flavonoids from wine and purple berries, as well as purple sweet potatoes, have been repeatedly shown to have beneficial effects. Similarly, the positive effects of niacin in the elderly have been repeatedly confirmed. But is this related to resveratrol?<ref>[https://youtu.be/Xn0EJQPyxkA?si=w5SS2Hdn-dxGBasF The David Sinclair $720,000,000 Train Wreck!]</ref>

	== References ==		== References ==

Andrea: /* Evidence of lifespan extension */

2023-02-24T21:09:04Z

Evidence of lifespan extension

← Older revision		Revision as of 21:09, 24 February 2023
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	== Evidence of lifespan extension ==		== Evidence of lifespan extension ==
	Resveratrol has been shown to extend healthy lifespan in yeast, worms, fruit flies, bees, and fish by 10-70%. <ref>Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., ... & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. ''Nature'', ''425''(6954), 191-196. https://doi.org/10.1038/nature01960</ref><ref>Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. ''Nature'', ''430''(7000), 686-689. https://doi.org/10.1038/nature02789</ref><ref>Rascón, B., Hubbard, B. P., Sinclair, D. A., & Amdam, G. V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. ''Aging (Albany NY)'', ''4''(7), 499. https://doi.org/10.18632/aging.100474</ref><ref>Valenzano, D. R., Terzibasi, E., Genade, T., Cattaneo, A., Domenici, L., & Cellerino, A. (2006). Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. ''Current biology'', ''16''(3), 296-300. https://doi.org/10.1016/j.cub.2005.12.038</ref><ref>Yu, X., & Li, G. (2012). Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri. ''Experimental gerontology'', ''47''(12), 940-949. https://doi.org/10.1016/j.exger.2012.08.009</ref> In mice on a high-calorie diet, resveratrol reduced the risk of death from the diet by 31%.<ref>Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. ''Nature'', ''444''(7117), 337-342. https://dx.doi.org/10.1038/nature05354</ref> However, ~~most~~ of these studies come from ~~David~~ Sinclair's lab ~~at Harvard University. Sinclair has~~ conflicting monetary interests given he was the founder of the company Sirtris Pharmaceuticals, a biotechnology company focused on using resveratrol and other potential [[Sirtuins\|sirtuin]] activators to extend human lifespan.<ref>https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm</ref>		Resveratrol has been shown to extend healthy lifespan in yeast, worms, fruit flies, bees, and fish by 10-70% <ref>Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., ... & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. ''Nature'', ''425''(6954), 191-196. https://doi.org/10.1038/nature01960</ref><ref>Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. ''Nature'', ''430''(7000), 686-689. https://doi.org/10.1038/nature02789</ref><ref>Rascón, B., Hubbard, B. P., Sinclair, D. A., & Amdam, G. V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. ''Aging (Albany NY)'', ''4''(7), 499. https://doi.org/10.18632/aging.100474</ref><ref>Valenzano, D. R., Terzibasi, E., Genade, T., Cattaneo, A., Domenici, L., & Cellerino, A. (2006). Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. ''Current biology'', ''16''(3), 296-300. https://doi.org/10.1016/j.cub.2005.12.038</ref><ref>Yu, X., & Li, G. (2012). Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri. ''Experimental gerontology'', ''47''(12), 940-949. https://doi.org/10.1016/j.exger.2012.08.009</ref> In mice on a high-calorie diet, resveratrol reduced the risk of death from the diet by 31%.<ref>Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. ''Nature'', ''444''(7117), 337-342. https://dx.doi.org/10.1038/nature05354</ref> However, many of these studies come from Sinclair's lab, which in the past had conflicting monetary interests given he was the founder of the company Sirtris Pharmaceuticals, a biotechnology company focused on using resveratrol and other potential [[Sirtuins\|sirtuin]] activators to extend human lifespan.<ref>https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm</ref>

	Independent laboratories demonstrated there is no lifespan extension in healthy mice and rats.<ref>Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., ... & de Cabo, R. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. ''Cell metabolism'', ''8''(2), 157-168. https://doi.org/10.1016/j.cmet.2008.06.011</ref><ref>Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., De Cabo, R., ... & Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. ''The Journals of Gerontology: Series A'', ''66''(2), 191-201. https://doi.org/10.1093/gerona/glq178</ref><ref>Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., De Cabo, R., Fernandez, E., ... & Harrison, D. E. (2013). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. ''Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences'', ''68''(1), 6-16. https://dx.doi.org/10.1093/gerona/gls070</ref><ref name=":4">da Luz, P. L., Tanaka, L., Brum, P. C., Dourado, P. M. M., Favarato, D., Krieger, J. E., & Laurindo, F. R. M. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. ''Atherosclerosis'', ''224''(1), 136-142. https://doi.org/10.1016/j.atherosclerosis.2012.06.007</ref> Resveratrol has been shown to delay aspects of vascular aging in rodents, improving aging-impaired cognitive function.<ref name=":4" /><ref>Gocmez, S. S., Gacar, N., Utkan, T., Gacar, G., Scarpace, P. J., & Tumer, N. (2016). Protective effects of resveratrol on aging-induced cognitive impairment in rats. ''Neurobiology of learning and memory'', ''131'', 131-136. https://doi.org/10.1016/j.nlm.2016.03.022</ref> However given the lack of evidence of resveratrol to extend lifespan in rodent models, it does not appear likely to produce meaningful benefit for human aging.		Independent laboratories demonstrated there is no lifespan extension in healthy mice and rats.<ref>Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., ... & de Cabo, R. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. ''Cell metabolism'', ''8''(2), 157-168. https://doi.org/10.1016/j.cmet.2008.06.011</ref><ref>Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., De Cabo, R., ... & Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. ''The Journals of Gerontology: Series A'', ''66''(2), 191-201. https://doi.org/10.1093/gerona/glq178</ref><ref>Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., De Cabo, R., Fernandez, E., ... & Harrison, D. E. (2013). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. ''Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences'', ''68''(1), 6-16. https://dx.doi.org/10.1093/gerona/gls070</ref><ref name=":4">da Luz, P. L., Tanaka, L., Brum, P. C., Dourado, P. M. M., Favarato, D., Krieger, J. E., & Laurindo, F. R. M. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. ''Atherosclerosis'', ''224''(1), 136-142. https://doi.org/10.1016/j.atherosclerosis.2012.06.007</ref> Resveratrol has been shown to delay aspects of vascular aging in rodents, improving aging-impaired cognitive function.<ref name=":4" /><ref>Gocmez, S. S., Gacar, N., Utkan, T., Gacar, G., Scarpace, P. J., & Tumer, N. (2016). Protective effects of resveratrol on aging-induced cognitive impairment in rats. ''Neurobiology of learning and memory'', ''131'', 131-136. https://doi.org/10.1016/j.nlm.2016.03.022</ref> However given the lack of evidence of resveratrol to extend lifespan in rodent models, it does not appear likely to produce meaningful benefit for human aging.

Andrea: category change

2022-12-27T16:39:17Z

category change

← Older revision		Revision as of 16:39, 27 December 2022
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	Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a compound produced naturally by various plants in response to injury or microbial infection. Its main dietary sources include grapes, blueberry, cranberry, peanuts, and legumes.<ref>Tian, B., & Liu, J. (2020). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. ''Journal of the Science of Food and Agriculture'', ''100''(4), 1392-1404. https://doi.org/10.1002/jsfa.10152</ref> Resveratrol has gained widespread attention, in part due to reports of its lifespan extension properties in a range of model organisms.<ref>Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. ''Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease'', ''1852''(6), 1209-1218. https://doi.org/10.1016/j.bbadis.2015.01.012</ref> However, there has also been significant controversy and criticism.<ref name=":6">Kaeberlein, M. (2010). Resveratrol and rapamycin: are they anti‐aging drugs?. ''Bioessays'', ''32''(2), 96-99.</ref> Resveratrol is currently considered a dietary supplement and is not an approved medicine.		Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a compound produced naturally by various plants in response to injury or microbial infection. Its main dietary sources include grapes, blueberry, cranberry, peanuts, and legumes.<ref>Tian, B., & Liu, J. (2020). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. ''Journal of the Science of Food and Agriculture'', ''100''(4), 1392-1404. https://doi.org/10.1002/jsfa.10152</ref> Resveratrol has gained widespread attention, in part due to reports of its lifespan extension properties in a range of model organisms.<ref>Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. ''Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease'', ''1852''(6), 1209-1218. https://doi.org/10.1016/j.bbadis.2015.01.012</ref> However, there has also been significant controversy and criticism.<ref name=":6">Kaeberlein, M. (2010). Resveratrol and rapamycin: are they anti‐aging drugs?. ''Bioessays'', ''32''(2), 96-99.</ref> Resveratrol is currently considered a dietary supplement and is not an approved medicine.

	As of today, resveratrol is known to have widespread effects in physiology but is not considered to be a lifespan extending agent.<ref>Pearson, K., Baur, J., Lewis, K., Peshkin, L., Price, N., & Labinskyy, N. et al. (2008). Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. ''Cell Metabolism'', ''8''(2), 157-168. doi: 10.1016/j.cmet.2008.06.011</ref> Additionally, despite years of widespread misinformation resveratrol has been debunked as a specific ''in vivo'' activator of the [[Sirtuins\|sirtuin]] protein SIR2.<ref name=":7">Beher, D., Wu, J., Cumine, S., Kim, K., Lu, S., Atangan, L., & Wang, M. (2009). Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity. ''Chemical Biology &Amp; Drug Design'', ''74''(6), 619-624. doi: 10.1111/j.1747-0285.2009.00901.x</ref><ref name=":8">Pacholec, M., Bleasdale, J., Chrunyk, B., Cunningham, D., Flynn, D., & Garofalo, R. et al. (2010). SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1. ''Journal Of Biological Chemistry'', ''285''(11), 8340-8351. doi: 10.1074/jbc.m109.088682</ref>		As of today, resveratrol is known to have widespread effects in physiology but is not considered to be a lifespan extending agent.<ref>Pearson, K., Baur, J., Lewis, K., Peshkin, L., Price, N., & Labinskyy, N. et al. (2008). Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. ''Cell Metabolism'', ''8''(2), 157-168. doi: 10.1016/j.cmet.2008.06.011</ref> Additionally, despite years of widespread misinformation resveratrol has been debunked as a specific ''in vivo'' activator of the [[Sirtuins\|sirtuin]] protein SIR2.<ref name=":7">Beher, D., Wu, J., Cumine, S., Kim, K., Lu, S., Atangan, L., & Wang, M. (2009). Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity. ''Chemical Biology &Amp; Drug Design'', ''74''(6), 619-624. doi: 10.1111/j.1747-0285.2009.00901.x</ref><ref name=":8">Pacholec, M., Bleasdale, J., Chrunyk, B., Cunningham, D., Flynn, D., & Garofalo, R. et al. (2010). SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1. ''Journal Of Biological Chemistry'', ''285''(11), [tel:8340-8351 8340-8351]. doi: 10.1074/jbc.m109.088682</ref>

	== Evidence of lifespan extension ==		== Evidence of lifespan extension ==
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	== Safety and bioavailability ==		== Safety and bioavailability ==
	It has been shown that resveratrol is generally safe in humans.<ref name=":0">Singh, A. P., Singh, R., Verma, S. S., Rai, V., Kaschula, C. H., Maiti, P., & Gupta, S. C. (2019). Health benefits of resveratrol: Evidence from clinical studies. ''Medicinal research reviews'', ''39''(5), 1851-1891. https://doi.org/10.1002/med.21565</ref><ref name=":1">Bitterman, J. L., & Chung, J. H. (2015). Metabolic effects of resveratrol: addressing the controversies. ''Cellular and Molecular Life Sciences'', ''72''(8), 1473-1488. https://doi.org/10.1007/s00018-014-1808-8</ref> Mild adverse effects such as nausea, diarrhea, and abdominal pain have been reported with doses of 1 g per day and higher.<ref>Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., ... & Brenner, D. E. (2010). Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. ''Cancer research'', ''70''(22), 9003-9011. https://doi.org/10.1158/0008-5472.can-10-2364</ref><ref>Patel, K. R., Scott, E., Brown, V. A., Gescher, A. J., Steward, W. P., & Brown, K. (2011). Clinical trials of resveratrol. ''Annals of the New York Academy of Sciences'', ''1215''(1), 161-169. https://doi.org/10.1111/j.1749-6632.2010.05853.x</ref>		It has been shown that resveratrol is generally safe in humans.<ref name=":0">Singh, A. P., Singh, R., Verma, S. S., Rai, V., Kaschula, C. H., Maiti, P., & Gupta, S. C. (2019). Health benefits of resveratrol: Evidence from clinical studies. ''Medicinal research reviews'', ''39''(5), 1851-1891. https://doi.org/10.1002/med.21565</ref><ref name=":1">Bitterman, J. L., & Chung, J. H. (2015). Metabolic effects of resveratrol: addressing the controversies. ''Cellular and Molecular Life Sciences'', ''72''(8), 1473-1488. https://doi.org/10.1007/s00018-014-1808-8</ref> Mild adverse effects such as nausea, diarrhea, and abdominal pain have been reported with doses of 1 g per day and higher.<ref>Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., ... & Brenner, D. E. (2010). Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. ''Cancer research'', ''70''(22), [tel:9003-9011 9003-9011]. https://doi.org/10.1158/0008-5472.can-10-2364</ref><ref>Patel, K. R., Scott, E., Brown, V. A., Gescher, A. J., Steward, W. P., & Brown, K. (2011). Clinical trials of resveratrol. ''Annals of the New York Academy of Sciences'', ''1215''(1), 161-169. https://doi.org/10.1111/j.1749-6632.2010.05853.x</ref>

	Resveratrol is quickly metabolized and is poorly absorbed in the human body, which limits its potential for clinical use in humans.<ref name=":0" />		Resveratrol is quickly metabolized and is poorly absorbed in the human body, which limits its potential for clinical use in humans.<ref name=":0" />
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	== References ==		== References ==
	<references />		<references />
	[[Category:~~Longevity~~]]		[[Category:Main list]]
	[[Category:~~Supplement~~]]		[[Category:Drugs]]

Andrea at 19:50, 30 November 2022

2022-11-30T19:50:21Z

← Older revision		Revision as of 19:50, 30 November 2022
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	== Evidence of lifespan extension ==		== Evidence of lifespan extension ==
	Resveratrol has been shown to extend healthy lifespan in yeast, worms, fruit flies, bees, and fish by 10-70%. <ref>Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., ... & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. ''Nature'', ''425''(6954), 191-196. https://doi.org/10.1038/nature01960</ref><ref>Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. ''Nature'', ''430''(7000), 686-689. https://doi.org/10.1038/nature02789</ref><ref>Rascón, B., Hubbard, B. P., Sinclair, D. A., & Amdam, G. V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. ''Aging (Albany NY)'', ''4''(7), 499. https://doi.org/10.18632/aging.100474</ref><ref>Valenzano, D. R., Terzibasi, E., Genade, T., Cattaneo, A., Domenici, L., & Cellerino, A. (2006). Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. ''Current biology'', ''16''(3), 296-300. https://doi.org/10.1016/j.cub.2005.12.038</ref><ref>Yu, X., & Li, G. (2012). Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri. ''Experimental gerontology'', ''47''(12), 940-949. https://doi.org/10.1016/j.exger.2012.08.009</ref> In mice on a high-calorie diet, resveratrol reduced the risk of death from the diet by 31%.<ref>Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. ''Nature'', ''444''(7117), 337-342. https://dx.doi.org/10.1038/nature05354</ref> However, most of these studies come from David Sinclair's lab at Harvard University. Sinclair has conflicting monetary interests given he was the founder of the company Sirtris Pharmaceuticals, a biotechnology company focused on using resveratrol and other potential sirtuin activators to extend human lifespan.<ref>https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm</ref>		Resveratrol has been shown to extend healthy lifespan in yeast, worms, fruit flies, bees, and fish by 10-70%. <ref>Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., ... & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. ''Nature'', ''425''(6954), 191-196. https://doi.org/10.1038/nature01960</ref><ref>Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. ''Nature'', ''430''(7000), 686-689. https://doi.org/10.1038/nature02789</ref><ref>Rascón, B., Hubbard, B. P., Sinclair, D. A., & Amdam, G. V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. ''Aging (Albany NY)'', ''4''(7), 499. https://doi.org/10.18632/aging.100474</ref><ref>Valenzano, D. R., Terzibasi, E., Genade, T., Cattaneo, A., Domenici, L., & Cellerino, A. (2006). Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. ''Current biology'', ''16''(3), 296-300. https://doi.org/10.1016/j.cub.2005.12.038</ref><ref>Yu, X., & Li, G. (2012). Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri. ''Experimental gerontology'', ''47''(12), 940-949. https://doi.org/10.1016/j.exger.2012.08.009</ref> In mice on a high-calorie diet, resveratrol reduced the risk of death from the diet by 31%.<ref>Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. ''Nature'', ''444''(7117), 337-342. https://dx.doi.org/10.1038/nature05354</ref> However, most of these studies come from David Sinclair's lab at Harvard University. Sinclair has conflicting monetary interests given he was the founder of the company Sirtris Pharmaceuticals, a biotechnology company focused on using resveratrol and other potential [[Sirtuins\|sirtuin]] activators to extend human lifespan.<ref>https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm</ref>

	Independent laboratories demonstrated there is no lifespan extension in healthy mice and rats.<ref>Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., ... & de Cabo, R. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. ''Cell metabolism'', ''8''(2), 157-168. https://doi.org/10.1016/j.cmet.2008.06.011</ref><ref>Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., De Cabo, R., ... & Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. ''The Journals of Gerontology: Series A'', ''66''(2), 191-201. https://doi.org/10.1093/gerona/glq178</ref><ref>Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., De Cabo, R., Fernandez, E., ... & Harrison, D. E. (2013). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. ''Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences'', ''68''(1), 6-16. https://dx.doi.org/10.1093/gerona/gls070</ref><ref name=":4">da Luz, P. L., Tanaka, L., Brum, P. C., Dourado, P. M. M., Favarato, D., Krieger, J. E., & Laurindo, F. R. M. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. ''Atherosclerosis'', ''224''(1), 136-142. https://doi.org/10.1016/j.atherosclerosis.2012.06.007</ref> Resveratrol has been shown to delay aspects of vascular aging in rodents, improving aging-impaired cognitive function.<ref name=":4" /><ref>Gocmez, S. S., Gacar, N., Utkan, T., Gacar, G., Scarpace, P. J., & Tumer, N. (2016). Protective effects of resveratrol on aging-induced cognitive impairment in rats. ''Neurobiology of learning and memory'', ''131'', 131-136. https://doi.org/10.1016/j.nlm.2016.03.022</ref> However given the lack of evidence of resveratrol to extend lifespan in rodent models, it does not appear likely to produce meaningful benefit for human aging.		Independent laboratories demonstrated there is no lifespan extension in healthy mice and rats.<ref>Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., ... & de Cabo, R. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. ''Cell metabolism'', ''8''(2), 157-168. https://doi.org/10.1016/j.cmet.2008.06.011</ref><ref>Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., De Cabo, R., ... & Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. ''The Journals of Gerontology: Series A'', ''66''(2), 191-201. https://doi.org/10.1093/gerona/glq178</ref><ref>Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., De Cabo, R., Fernandez, E., ... & Harrison, D. E. (2013). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. ''Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences'', ''68''(1), 6-16. https://dx.doi.org/10.1093/gerona/gls070</ref><ref name=":4">da Luz, P. L., Tanaka, L., Brum, P. C., Dourado, P. M. M., Favarato, D., Krieger, J. E., & Laurindo, F. R. M. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. ''Atherosclerosis'', ''224''(1), 136-142. https://doi.org/10.1016/j.atherosclerosis.2012.06.007</ref> Resveratrol has been shown to delay aspects of vascular aging in rodents, improving aging-impaired cognitive function.<ref name=":4" /><ref>Gocmez, S. S., Gacar, N., Utkan, T., Gacar, G., Scarpace, P. J., & Tumer, N. (2016). Protective effects of resveratrol on aging-induced cognitive impairment in rats. ''Neurobiology of learning and memory'', ''131'', 131-136. https://doi.org/10.1016/j.nlm.2016.03.022</ref> However given the lack of evidence of resveratrol to extend lifespan in rodent models, it does not appear likely to produce meaningful benefit for human aging.

Andrea: /* */

2022-08-29T17:46:41Z

← Older revision		Revision as of 17:46, 29 August 2022
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	Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a compound produced naturally by various plants in response to injury or microbial infection. Its main dietary sources include grapes, blueberry, cranberry, peanuts, and legumes.<ref>Tian, B., & Liu, J. (2020). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. ''Journal of the Science of Food and Agriculture'', ''100''(4), 1392-1404. https://doi.org/10.1002/jsfa.10152</ref> Resveratrol has gained widespread attention, in part due to reports of its lifespan extension properties in a range of model organisms.<ref>Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. ''Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease'', ''1852''(6), 1209-1218. https://doi.org/10.1016/j.bbadis.2015.01.012</ref> However, there has also been significant controversy and criticism.<ref name=":6">Kaeberlein, M. (2010). Resveratrol and rapamycin: are they anti‐aging drugs?. ''Bioessays'', ''32''(2), 96-99.</ref> Resveratrol is currently considered a dietary supplement and is not an approved medicine.		Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a compound produced naturally by various plants in response to injury or microbial infection. Its main dietary sources include grapes, blueberry, cranberry, peanuts, and legumes.<ref>Tian, B., & Liu, J. (2020). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. ''Journal of the Science of Food and Agriculture'', ''100''(4), 1392-1404. https://doi.org/10.1002/jsfa.10152</ref> Resveratrol has gained widespread attention, in part due to reports of its lifespan extension properties in a range of model organisms.<ref>Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. ''Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease'', ''1852''(6), 1209-1218. https://doi.org/10.1016/j.bbadis.2015.01.012</ref> However, there has also been significant controversy and criticism.<ref name=":6">Kaeberlein, M. (2010). Resveratrol and rapamycin: are they anti‐aging drugs?. ''Bioessays'', ''32''(2), 96-99.</ref> Resveratrol is currently considered a dietary supplement and is not an approved medicine.

	As of today, resveratrol is known to have widespread effects in physiology but is not considered to be a lifespan extending agent.<ref>Pearson, K., Baur, J., Lewis, K., Peshkin, L., Price, N., & Labinskyy, N. et al. (2008). Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. ''Cell Metabolism'', ''8''(2), 157-168. doi: 10.1016/j.cmet.2008.06.011</ref> Additionally, despite years of widespread misinformation resveratrol has been debunked as a specific activator of the [[Sirtuins\|sirtuin]] protein SIR2 ~~''in vivo''~~.<ref name=":7">Beher, D., Wu, J., Cumine, S., Kim, K., Lu, S., Atangan, L., & Wang, M. (2009). Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity. ''Chemical Biology &Amp; Drug Design'', ''74''(6), 619-624. doi: 10.1111/j.1747-0285.2009.00901.x</ref><ref name=":8">Pacholec, M., Bleasdale, J., Chrunyk, B., Cunningham, D., Flynn, D., & Garofalo, R. et al. (2010). SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1. ''Journal Of Biological Chemistry'', ''285''(11), 8340-8351. doi: 10.1074/jbc.m109.088682</ref>		As of today, resveratrol is known to have widespread effects in physiology but is not considered to be a lifespan extending agent.<ref>Pearson, K., Baur, J., Lewis, K., Peshkin, L., Price, N., & Labinskyy, N. et al. (2008). Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. ''Cell Metabolism'', ''8''(2), 157-168. doi: 10.1016/j.cmet.2008.06.011</ref> Additionally, despite years of widespread misinformation resveratrol has been debunked as a specific ''in vivo'' activator of the [[Sirtuins\|sirtuin]] protein SIR2.<ref name=":7">Beher, D., Wu, J., Cumine, S., Kim, K., Lu, S., Atangan, L., & Wang, M. (2009). Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity. ''Chemical Biology &Amp; Drug Design'', ''74''(6), 619-624. doi: 10.1111/j.1747-0285.2009.00901.x</ref><ref name=":8">Pacholec, M., Bleasdale, J., Chrunyk, B., Cunningham, D., Flynn, D., & Garofalo, R. et al. (2010). SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1. ''Journal Of Biological Chemistry'', ''285''(11), 8340-8351. doi: 10.1074/jbc.m109.088682</ref>

	== Evidence of lifespan extension ==		== Evidence of lifespan extension ==

Andrea: /* Completed article */

2022-08-29T17:45:46Z

Completed article

Show changes

Andrea: /* Safety and bioavailability */

2022-08-06T12:43:16Z

Safety and bioavailability

← Older revision		Revision as of 12:43, 6 August 2022
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	== Mechanism ==		== Mechanism ==
	Resveratrol most likely acts through multiple mechanisms in the cell. Silent Information Regulator 1 (SIRT1) protein was initially suggested as one of its targets.<ref name=":0" /> Resveratrol was proposed to induce SIRT1 either directly or through phosphorylation of AMP-activated protein kinase (AMPK). Upon induction, SIRT1 has been shown to modulate activity of molecules taking part in stimulating mitochondrial biogenesis, vasodilation, antioxidant defence, glucose and lipid homeostasis, as well as those inhibiting inflammation.<ref name=":2" /><ref name=":3" />		Resveratrol most likely acts through multiple mechanisms in the cell via [[sirtuins]]. Silent Information Regulator 1 (SIRT1) protein was initially suggested as one of its targets.<ref name=":0" /> Resveratrol was proposed to induce SIRT1 either directly or through phosphorylation of AMP-activated protein kinase (AMPK). Upon induction, SIRT1 has been shown to modulate activity of molecules taking part in stimulating mitochondrial biogenesis, vasodilation, antioxidant defence, glucose and lipid homeostasis, as well as those inhibiting inflammation.<ref name=":2" /><ref name=":3" />

	Whether resveratrol directly activates SIRT1 is controversial, with a number of studies failing to observe activation or interaction between the two molecules. <ref>Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S. C., Atangan, L., & Wang, M. (2009). Resveratrol is not a direct activator of SIRT1 enzyme activity. ''Chemical biology & drug design'', ''74''(6), 619-624. https://doi.org/10.1111/j.1747-0285.2009.00901.x</ref><ref name=":5">Benslimane, Y., Bertomeu, T., Coulombe-Huntington, J., McQuaid, M., Sánchez-Osuna, M., Papadopoli, D., ... & Harrington, L. (2020). Genome-wide screens reveal that resveratrol induces replicative stress in human cells. ''Molecular Cell'', ''79''(5), 846-856. https://doi.org/10.1016/j.molcel.2020.07.010</ref> Alternative modes of action for resveratrol have been suggested, such as introduction of replication stress in a cell.<ref name=":5" />		Whether resveratrol directly activates SIRT1 is controversial, with a number of studies failing to observe activation or interaction between the two molecules. <ref>Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S. C., Atangan, L., & Wang, M. (2009). Resveratrol is not a direct activator of SIRT1 enzyme activity. ''Chemical biology & drug design'', ''74''(6), 619-624. https://doi.org/10.1111/j.1747-0285.2009.00901.x</ref><ref name=":5">Benslimane, Y., Bertomeu, T., Coulombe-Huntington, J., McQuaid, M., Sánchez-Osuna, M., Papadopoli, D., ... & Harrington, L. (2020). Genome-wide screens reveal that resveratrol induces replicative stress in human cells. ''Molecular Cell'', ''79''(5), 846-856. https://doi.org/10.1016/j.molcel.2020.07.010</ref> Alternative modes of action for resveratrol have been suggested, such as introduction of replication stress in a cell.<ref name=":5" />

Geroscientist at 22:46, 15 December 2021

2021-12-15T22:46:49Z

← Older revision		Revision as of 22:46, 15 December 2021
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	== Mechanism ==		== Mechanism ==
	Resveratrol most likely acts through multiple mechanisms in the cell. Silent Information Regulator 1 (SIRT1) protein was initially suggested as one of its ~~crucial~~ targets.<ref name=":0" /> Resveratrol was proposed to induce SIRT1 either directly or through phosphorylation of AMP-activated protein kinase (AMPK). Upon induction, SIRT1 has been shown to modulate activity of molecules taking part in stimulating mitochondrial biogenesis, vasodilation, antioxidant defence, glucose and lipid homeostasis, as well as those inhibiting inflammation.<ref name=":2" /><ref name=":3" />		Resveratrol most likely acts through multiple mechanisms in the cell. Silent Information Regulator 1 (SIRT1) protein was initially suggested as one of its targets.<ref name=":0" /> Resveratrol was proposed to induce SIRT1 either directly or through phosphorylation of AMP-activated protein kinase (AMPK). Upon induction, SIRT1 has been shown to modulate activity of molecules taking part in stimulating mitochondrial biogenesis, vasodilation, antioxidant defence, glucose and lipid homeostasis, as well as those inhibiting inflammation.<ref name=":2" /><ref name=":3" />

	~~Direct activation of~~ SIRT1 ~~by resveratrol~~ is ~~being debated~~, with a number of studies failing to observe ~~the~~ activation or interaction between the two molecules. <ref>Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S. C., Atangan, L., & Wang, M. (2009). Resveratrol is not a direct activator of SIRT1 enzyme activity. ''Chemical biology & drug design'', ''74''(6), 619-624. https://doi.org/10.1111/j.1747-0285.2009.00901.x</ref><ref name=":5">Benslimane, Y., Bertomeu, T., Coulombe-Huntington, J., McQuaid, M., Sánchez-Osuna, M., Papadopoli, D., ... & Harrington, L. (2020). Genome-wide screens reveal that resveratrol induces replicative stress in human cells. ''Molecular Cell'', ''79''(5), 846-856. https://doi.org/10.1016/j.molcel.2020.07.010</ref> Alternative modes of action for resveratrol have been suggested, such as introduction of replication stress in a cell.<ref name=":5" />		Whether resveratrol directly activates SIRT1 is controversial, with a number of studies failing to observe activation or interaction between the two molecules. <ref>Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S. C., Atangan, L., & Wang, M. (2009). Resveratrol is not a direct activator of SIRT1 enzyme activity. ''Chemical biology & drug design'', ''74''(6), 619-624. https://doi.org/10.1111/j.1747-0285.2009.00901.x</ref><ref name=":5">Benslimane, Y., Bertomeu, T., Coulombe-Huntington, J., McQuaid, M., Sánchez-Osuna, M., Papadopoli, D., ... & Harrington, L. (2020). Genome-wide screens reveal that resveratrol induces replicative stress in human cells. ''Molecular Cell'', ''79''(5), 846-856. https://doi.org/10.1016/j.molcel.2020.07.010</ref> Alternative modes of action for resveratrol have been suggested, such as introduction of replication stress in a cell.<ref name=":5" />

	== Derivatives of resveratrol and drug development attempts ==		== Derivatives of resveratrol and drug development attempts ==

Geroscientist at 04:26, 14 December 2021

2021-12-14T04:26:59Z

Geroscientist: /* Derivatives of resveratrol and drug development attempts */

2021-12-14T02:25:59Z

Derivatives of resveratrol and drug development attempts

← Older revision		Revision as of 02:25, 14 December 2021
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	== Derivatives of resveratrol and drug development attempts ==		== Derivatives of resveratrol and drug development attempts ==
	In 2004 a company Sirtris Pharmaceuticals, Inc. was conceived to study potential of resveratrol as a drug for type 2 diabetes, cancer, and other diseases. The company's initial product was called SRT501, and was a formulation of reservatrol. In 2008 Sirtris was purchased by GlaxoSmithKline. ~~Works on~~ SRT501 were terminated in 2010, due to its side effects and lack of specificity to SIRT1, followed by ~~shut down~~ of Sirtis in 2013. <ref>Popat, R., Plesner, T., Davies, F., Cook, G., Cook, M., Elliott, P., ... & Cavenagh, J. (2012). A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. ''British journal of haematology'', ''160''(5), 714-717. https://doi.org/10.1111/bjh.12154 </ref>		In 2004 a company Sirtris Pharmaceuticals, Inc. was conceived to study potential of resveratrol as a drug for type 2 diabetes, cancer, and other diseases. The company's initial product was called SRT501, and was a formulation of reservatrol. In 2008 Sirtris was purchased by the pharmaceutical company GlaxoSmithKline. Further development of SRT501 were terminated in 2010, in part due to its side effects and lack of specificity to SIRT1, followed by shutdown of Sirtis in 2013. <ref>Popat, R., Plesner, T., Davies, F., Cook, G., Cook, M., Elliott, P., ... & Cavenagh, J. (2012). A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. ''British journal of haematology'', ''160''(5), 714-717. https://doi.org/10.1111/bjh.12154 </ref>

	== References ==		== References ==

← Older revision		Revision as of 04:26, 14 December 2021
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	[[File:Resveratrol.png\|thumb\|200x200px\|The chemical structure of trans-resveratrol.]]		[[File:Resveratrol.png\|thumb\|200x200px\|The chemical structure of trans-resveratrol.]]
	Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a compound produced naturally by various plants in response to injury or microbial infection. Its main dietary sources include grapes, blueberry, cranberry, peanuts, and legumes.<ref>Tian, B., & Liu, J. (2020). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. ''Journal of the Science of Food and Agriculture'', ''100''(4), 1392-1404. https://doi.org/10.1002/jsfa.10152</ref> Resveratrol has gained widespread ~~scientific~~ attention ~~after~~ reports of its lifespan extension properties in a range of model organisms.<ref>Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. ''Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease'', ''1852''(6), 1209-1218. https://doi.org/10.1016/j.bbadis.2015.01.012</ref> Resveratrol is currently considered a dietary supplement and is not an approved medicine.		Resveratrol (trans‐3,5,4′‐trihydroxystilbene) is a compound produced naturally by various plants in response to injury or microbial infection. Its main dietary sources include grapes, blueberry, cranberry, peanuts, and legumes.<ref>Tian, B., & Liu, J. (2020). Resveratrol: A review of plant sources, synthesis, stability, modification and food application. ''Journal of the Science of Food and Agriculture'', ''100''(4), 1392-1404. https://doi.org/10.1002/jsfa.10152</ref> Resveratrol has gained widespread attention, in part due to reports of its lifespan extension properties in a range of model organisms.<ref>Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. ''Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease'', ''1852''(6), 1209-1218. https://doi.org/10.1016/j.bbadis.2015.01.012</ref> However, there has also been significant controversy and criticism.<ref name=":6">Kaeberlein, M. (2010). Resveratrol and rapamycin: are they anti‐aging drugs?. ''Bioessays'', ''32''(2), 96-99.</ref> Resveratrol is currently considered a dietary supplement and is not an approved medicine.

	== Evidence of lifespan extension ==		== Evidence of lifespan extension ==
	Resveratrol has been shown to extend healthy lifespan in yeast, worms, fruit flies, bees, and fish by 10-70%. <ref>Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., ... & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. ''Nature'', ''425''(6954), 191-196. https://doi.org/10.1038/nature01960</ref><ref>Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. ''Nature'', ''430''(7000), 686-689. https://doi.org/10.1038/nature02789</ref><ref>Rascón, B., Hubbard, B. P., Sinclair, D. A., & Amdam, G. V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. ''Aging (Albany NY)'', ''4''(7), 499. https://doi.org/10.18632/aging.100474</ref><ref>Valenzano, D. R., Terzibasi, E., Genade, T., Cattaneo, A., Domenici, L., & Cellerino, A. (2006). Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. ''Current biology'', ''16''(3), 296-300. https://doi.org/10.1016/j.cub.2005.12.038</ref><ref>Yu, X., & Li, G. (2012). Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri. ''Experimental gerontology'', ''47''(12), 940-949. https://doi.org/10.1016/j.exger.2012.08.009</ref> In mice on a high-calorie diet, resveratrol reduced the risk of death from the diet by 31%.<ref>Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. ''Nature'', ''444''(7117), 337-342. https://dx.doi.org/10.1038/nature05354</ref>		Resveratrol has been shown to extend healthy lifespan in yeast, worms, fruit flies, bees, and fish by 10-70%. <ref>Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., ... & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. ''Nature'', ''425''(6954), 191-196. https://doi.org/10.1038/nature01960</ref><ref>Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. ''Nature'', ''430''(7000), 686-689. https://doi.org/10.1038/nature02789</ref><ref>Rascón, B., Hubbard, B. P., Sinclair, D. A., & Amdam, G. V. (2012). The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. ''Aging (Albany NY)'', ''4''(7), 499. https://doi.org/10.18632/aging.100474</ref><ref>Valenzano, D. R., Terzibasi, E., Genade, T., Cattaneo, A., Domenici, L., & Cellerino, A. (2006). Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. ''Current biology'', ''16''(3), 296-300. https://doi.org/10.1016/j.cub.2005.12.038</ref><ref>Yu, X., & Li, G. (2012). Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri. ''Experimental gerontology'', ''47''(12), 940-949. https://doi.org/10.1016/j.exger.2012.08.009</ref> In mice on a high-calorie diet, resveratrol reduced the risk of death from the diet by 31%.<ref>Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. ''Nature'', ''444''(7117), 337-342. https://dx.doi.org/10.1038/nature05354</ref>

	No lifespan extension has been observed in healthy mice and rats.<ref>Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., ... & de Cabo, R. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. ''Cell metabolism'', ''8''(2), 157-168. https://doi.org/10.1016/j.cmet.2008.06.011</ref><ref>Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., De Cabo, R., ... & Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. ''The Journals of Gerontology: Series A'', ''66''(2), 191-201. https://doi.org/10.1093/gerona/glq178</ref><ref>Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., De Cabo, R., Fernandez, E., ... & Harrison, D. E. (2013). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. ''Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences'', ''68''(1), 6-16. https://dx.doi.org/10.1093/gerona/gls070</ref><ref name=":4">da Luz, P. L., Tanaka, L., Brum, P. C., Dourado, P. M. M., Favarato, D., Krieger, J. E., & Laurindo, F. R. M. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. ''Atherosclerosis'', ''224''(1), 136-142. https://doi.org/10.1016/j.atherosclerosis.2012.06.007</ref> Resveratrol has been shown to delay aspects of vascular aging in rodents, improving aging-impaired cognitive function.<ref name=":4" /><ref>Gocmez, S. S., Gacar, N., Utkan, T., Gacar, G., Scarpace, P. J., & Tumer, N. (2016). Protective effects of resveratrol on aging-induced cognitive impairment in rats. ''Neurobiology of learning and memory'', ''131'', 131-136. https://doi.org/10.1016/j.nlm.2016.03.022</ref> Given the ~~inability~~ of resveratrol to extend lifespan in rodent models, it does not appear likely to produce meaningful benefit for human aging. ~~Evidence~~ for human lifespan extension will need to be shown in large, randomized controlled trials.		No lifespan extension has been observed in healthy mice and rats.<ref>Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., ... & de Cabo, R. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. ''Cell metabolism'', ''8''(2), 157-168. https://doi.org/10.1016/j.cmet.2008.06.011</ref><ref>Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., De Cabo, R., ... & Strong, R. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. ''The Journals of Gerontology: Series A'', ''66''(2), 191-201. https://doi.org/10.1093/gerona/glq178</ref><ref>Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., De Cabo, R., Fernandez, E., ... & Harrison, D. E. (2013). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. ''Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences'', ''68''(1), 6-16. https://dx.doi.org/10.1093/gerona/gls070</ref><ref name=":4">da Luz, P. L., Tanaka, L., Brum, P. C., Dourado, P. M. M., Favarato, D., Krieger, J. E., & Laurindo, F. R. M. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. ''Atherosclerosis'', ''224''(1), 136-142. https://doi.org/10.1016/j.atherosclerosis.2012.06.007</ref> Resveratrol has been shown to delay aspects of vascular aging in rodents, improving aging-impaired cognitive function.<ref name=":4" /><ref>Gocmez, S. S., Gacar, N., Utkan, T., Gacar, G., Scarpace, P. J., & Tumer, N. (2016). Protective effects of resveratrol on aging-induced cognitive impairment in rats. ''Neurobiology of learning and memory'', ''131'', 131-136. https://doi.org/10.1016/j.nlm.2016.03.022</ref> Given the lack of evidence of resveratrol to extend lifespan in rodent models, it does not appear likely to produce meaningful benefit for human aging.

			Currently, it is unclear whether resveratrol will exert meaningful biological effects in humans.<ref name=":6" /> This is an ongoing area of research, but evidence for human lifespan extension will need to be shown in large, randomized controlled trials.

	== Human clinical trials ==		== Human clinical trials ==
	A range of clinical trials investigating the health benefits of resveratrol supplementation has been performed, some carrying conflicting results.<ref name=":0" /><ref name=":1" /> Resveratrol has been shown to improve glucose control and insulin sensitivity in persons with type 2 diabetes, and modulate some cancer-related genes.<ref>Liu, K., Zhou, R., Wang, B., & Mi, M. T. (2014). Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. ''The American journal of clinical nutrition'', ''99''(6), 1510-1519. https://doi.org/10.3945/ajcn.113.082024</ref><ref>Zhu, X., Wu, C., Qiu, S., Yuan, X., & Li, L. (2017). Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: Systematic review and meta-analysis. ''Nutrition & metabolism'', ''14''(1), 1-10. https://doi.org/10.1186/s12986-017-0217-z</ref><ref>Ko, J. H., Sethi, G., Um, J. Y., Shanmugam, M. K., Arfuso, F., Kumar, A. P., ... & Ahn, K. S. (2017). The role of resveratrol in cancer therapy. ''International journal of molecular sciences'', ''18''(12), 2589. https://dx.doi.org/10.3390/ijms18122589</ref> Resveratrol supplementation in postmenopausal women (150 mg per day for 12 months) resulted in improvement of overall cognitive performance.<ref>Zaw, J. J. T., Howe, P. R., & Wong, R. H. (2020). Sustained cerebrovascular and cognitive benefits of resveratrol in postmenopausal women. ''Nutrients'', ''12''(3), 828. https://doi.org/10.3390/nu12030828</ref> The study ~~concluded~~ that resveratrol supplementation could potentially reverse cognitive ageing by up to 10 years.		A range of clinical trials investigating the health benefits of resveratrol supplementation has been performed, some carrying conflicting results.<ref name=":0" /><ref name=":1" /> Resveratrol has been shown to improve glucose control and insulin sensitivity in persons with type 2 diabetes, and modulate some cancer-related genes.<ref>Liu, K., Zhou, R., Wang, B., & Mi, M. T. (2014). Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. ''The American journal of clinical nutrition'', ''99''(6), 1510-1519. https://doi.org/10.3945/ajcn.113.082024</ref><ref>Zhu, X., Wu, C., Qiu, S., Yuan, X., & Li, L. (2017). Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: Systematic review and meta-analysis. ''Nutrition & metabolism'', ''14''(1), 1-10. https://doi.org/10.1186/s12986-017-0217-z</ref><ref>Ko, J. H., Sethi, G., Um, J. Y., Shanmugam, M. K., Arfuso, F., Kumar, A. P., ... & Ahn, K. S. (2017). The role of resveratrol in cancer therapy. ''International journal of molecular sciences'', ''18''(12), 2589. https://dx.doi.org/10.3390/ijms18122589</ref> Resveratrol supplementation in postmenopausal women (150 mg per day for 12 months) resulted in improvement of overall cognitive performance.<ref>Zaw, J. J. T., Howe, P. R., & Wong, R. H. (2020). Sustained cerebrovascular and cognitive benefits of resveratrol in postmenopausal women. ''Nutrients'', ''12''(3), 828. https://doi.org/10.3390/nu12030828</ref> The study suggested that resveratrol supplementation could potentially reverse cognitive ageing by up to 10 years.

	== Safety and bioavailability ==		== Safety and bioavailability ==
Line 14:		Line 16:
	It has been shown that resveratrol is generally safe in humans.<ref name=":0">Singh, A. P., Singh, R., Verma, S. S., Rai, V., Kaschula, C. H., Maiti, P., & Gupta, S. C. (2019). Health benefits of resveratrol: Evidence from clinical studies. ''Medicinal research reviews'', ''39''(5), 1851-1891. https://doi.org/10.1002/med.21565</ref><ref name=":1">Bitterman, J. L., & Chung, J. H. (2015). Metabolic effects of resveratrol: addressing the controversies. ''Cellular and Molecular Life Sciences'', ''72''(8), 1473-1488. https://doi.org/10.1007/s00018-014-1808-8</ref> Mild adverse effects such as nausea, diarrhea, and abdominal pain have been reported with doses of 1 g per day and higher.<ref>Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., ... & Brenner, D. E. (2010). Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. ''Cancer research'', ''70''(22), 9003-9011. https://doi.org/10.1158/0008-5472.can-10-2364</ref><ref>Patel, K. R., Scott, E., Brown, V. A., Gescher, A. J., Steward, W. P., & Brown, K. (2011). Clinical trials of resveratrol. ''Annals of the New York Academy of Sciences'', ''1215''(1), 161-169. https://doi.org/10.1111/j.1749-6632.2010.05853.x</ref>		It has been shown that resveratrol is generally safe in humans.<ref name=":0">Singh, A. P., Singh, R., Verma, S. S., Rai, V., Kaschula, C. H., Maiti, P., & Gupta, S. C. (2019). Health benefits of resveratrol: Evidence from clinical studies. ''Medicinal research reviews'', ''39''(5), 1851-1891. https://doi.org/10.1002/med.21565</ref><ref name=":1">Bitterman, J. L., & Chung, J. H. (2015). Metabolic effects of resveratrol: addressing the controversies. ''Cellular and Molecular Life Sciences'', ''72''(8), 1473-1488. https://doi.org/10.1007/s00018-014-1808-8</ref> Mild adverse effects such as nausea, diarrhea, and abdominal pain have been reported with doses of 1 g per day and higher.<ref>Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., ... & Brenner, D. E. (2010). Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. ''Cancer research'', ''70''(22), 9003-9011. https://doi.org/10.1158/0008-5472.can-10-2364</ref><ref>Patel, K. R., Scott, E., Brown, V. A., Gescher, A. J., Steward, W. P., & Brown, K. (2011). Clinical trials of resveratrol. ''Annals of the New York Academy of Sciences'', ''1215''(1), 161-169. https://doi.org/10.1111/j.1749-6632.2010.05853.x</ref>

	Resveratrol is quickly metabolized and is poorly absorbed in the human body, which limits its potential for clinical use.<ref name=":0" />		Resveratrol is quickly metabolized and is poorly absorbed in the human body, which limits its potential for clinical use in humans.<ref name=":0" />

	== Mechanism ==		== Mechanism ==