Sirtuins - Revision history

TheNMNguy at 21:27, 5 June 2020

2020-06-05T21:27:49Z

TheNMNguy at 21:26, 5 June 2020

2020-06-05T21:26:30Z

TheNMNguy at 21:19, 5 June 2020

2020-06-05T21:19:46Z

TheNMNguy at 21:16, 5 June 2020

2020-06-05T21:16:07Z

TheNMNguy at 21:15, 5 June 2020

2020-06-05T21:15:18Z

TheNMNguy at 20:12, 5 June 2020

2020-06-05T20:12:10Z

TheNMNguy at 20:04, 5 June 2020

2020-06-05T20:04:31Z

TheNMNguy at 20:44, 4 June 2020

2020-06-04T20:44:04Z

TheNMNguy at 20:37, 4 June 2020

2020-06-04T20:37:48Z

TheNMNguy: Minor edits, will send comments to Brett

2020-06-04T20:10:22Z

Minor edits, will send comments to Brett

@@ Line 90: / Line 90: @@
 ===SIRT7===
 Mice lacking SIRT7 age prematurely and have heart complications, lethal heart hypertrophy.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Olesya Vakhrusheva, Christian Smolka, Praveen Gajawada, Sawa Kostin, Thomas Boettger, Thomas Kubin, Thomas Braun, Eva Bober.  '''Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice'''.  ''Circ Res'', 2008; 102(6): 703-710.</ref>
 ==Research==

@@ Line 85: / Line 85: @@
 Research using mice lacking SIRT6 provide the first evidence that sirtuins are involved in regulating mammalian aging. With reduced levels of SIRT6, mice fail to reach a normal lifespan.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Three weeks after birth, these mice exhibit premature aging and degeneration, which results in death around the fourth week of life.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Mice without SIRT6 are also smaller than ‘normal’ individuals.
 ===SIRT7===
 Mice lacking SIRT7 age prematurely and have heart complications, lethal heart hypertrophy.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Olesya Vakhrusheva, Christian Smolka, Praveen Gajawada, Sawa Kostin, Thomas Boettger, Thomas Kubin, Thomas Braun, Eva Bober.  '''Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice'''.  ''Circ Res'', 2008; 102(6): 703-710.</ref>

@@ Line 223: / Line 223: @@
 The use of nicotinamide adenine dinucleotide (NAD+)-boosting molecules, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), also constitute a way to improve sirtuin function. Since the actions of sirtuins depend on availability of NAD+ and since NAD+ levels decrease with age, some have started taking NMN and NR to boost sirtuin function by increasing NAD+ levels.
-Functional food is a promising method for anti-aging interventions. Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging.
+Functional food is a promising method for anti-aging interventions. Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging. Some of these functional foods include green vegetables, soy foods such as tofu, green tea, olive oil, and turmeric.
 ==Further reading==

@@ Line 221: / Line 221: @@
 Yi Wang, Xxinying Liang, Yaqi Chen, Xiaoping Zhao.  '''Screening SIRT1 activators from medicinal plants as bioactive compounds against oxidative damage in mitochondrial function'''.  ''Oxid Med Cell Longev'', 2016; DOI: 10.1155/2016/4206392.</ref> Activating sirtuins through the regulation of NAD+ levels offers an alternative method of stimulating sirtuin function.
-The use of nicotinamide adenine dinucleotide (NAD+)-boosting molecules, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), also constitute ways to improve sirtuin function. Since the actions of sirtuins depend on availability of NAD+ and since NAD+ levels decrease with age, some have started taking NMN and NR to boost sirtuin function by increasing NAD+ levels.
+The use of nicotinamide adenine dinucleotide (NAD+)-boosting molecules, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), also constitute a way to improve sirtuin function. Since the actions of sirtuins depend on availability of NAD+ and since NAD+ levels decrease with age, some have started taking NMN and NR to boost sirtuin function by increasing NAD+ levels.
 Functional food is a promising method for anti-aging interventions. Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging.

← Older revision		Revision as of 21:15, 5 June 2020
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	Yi Wang, Xxinying Liang, Yaqi Chen, Xiaoping Zhao. '''Screening SIRT1 activators from medicinal plants as bioactive compounds against oxidative damage in mitochondrial function'''. ''Oxid Med Cell Longev'', 2016; DOI: 10.1155/2016/4206392.</ref> Activating sirtuins through the regulation of NAD+ levels offers an alternative method of stimulating sirtuin function.		Yi Wang, Xxinying Liang, Yaqi Chen, Xiaoping Zhao. '''Screening SIRT1 activators from medicinal plants as bioactive compounds against oxidative damage in mitochondrial function'''. ''Oxid Med Cell Longev'', 2016; DOI: 10.1155/2016/4206392.</ref> Activating sirtuins through the regulation of NAD+ levels offers an alternative method of stimulating sirtuin function.
		+
		+	The use of nicotinamide adenine dinucleotide (NAD+)-boosting molecules, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), also constitute ways to improve sirtuin function. Since the actions of sirtuins depend on availability of NAD+ and since NAD+ levels decrease with age, some have started taking NMN and NR to boost sirtuin function by increasing NAD+ levels.

	Functional food is a promising method for anti-aging interventions. Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging.		Functional food is a promising method for anti-aging interventions. Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging.

@@ Line 76: / Line 76: @@
 ===SIRT2===
 SIRT2 levels may be a marker of obesity. In obese individuals, the levels of the protein drops in fat tissue.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Jaya Krishnan, Carsten Danzer, Tatiana Simka, Josef Ukropec, Katharina Manuela Walter, Susann Kumpf, Peter Mirtschink, Barbara Ukropcova, Daniela Gasperikova, Thierry Pedrazzini, Wilhelm Krek.  '''Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system'''.  ''Genes Dev'', 2012; DOI: 10.1101/gad.180406.111.</ref> In mice undergoing calorie restriction, SIRT2 levels increase in white fat tissue and kidneys.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Fei Wang, Margaret Nguyen, F. Xiao-Feng Qin, Qiang Tong.  '''SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction'''.  ''Aging Cell'', 2007; 6: 505-514.</ref>
 ===SIRT3===

@@ Line 32: / Line 32: @@
 Cell cycle regulation
 Mitochondrial function
-Ocidative stress
+Oxidative stress
 Centenarian-linked SNP
 |-
@@ Line 62: / Line 62: @@
 Stress resistance
 Apoptosis
-|} <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.</ref>
+|} <ref name=":0">Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.</ref>
@@ Line 72: / Line 72: @@
 SIRT1 plays a pivotal role in early development as well. In mice without SIRT1, only 20% reach maturity.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> The mice without SIRT1 are sterile, smaller than normal, and develop slower compared to normal mice.<ref>Hwei-Ling Cheng, Raul Mostoslavsky, Shin’ichi Saito, John P. Manis, Yansong Gu, Parin Patel, Roderick Bronson, Ettore Appella, Frederick W. Alt, Katrin F. Chua.  '''Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice'''.  ''Proc Natl Acad Sci U S A'', 2003; DOI: 10.1073/pna.1934713100. Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Michael W. McBurney, Xiaofeng Yang, Karen Jardine, Mary Hixon, Kim Boekelheide, John R. Webb, Peter M. Lansdorp, Madeleine Lemieux.  '''The mammalian SIR2α protein has a role in embryogenesis and gametogenesis'''.  ''Mol Cell Biol'', 2003; DOI: 10.1128/MCB.23.1.38-54.2003.</ref>
 ===SIRT2===
 SIRT2 levels may be a marker of obesity. In obese individuals, the levels of the protein drops in fat tissue.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Jaya Krishnan, Carsten Danzer, Tatiana Simka, Josef Ukropec, Katharina Manuela Walter, Susann Kumpf, Peter Mirtschink, Barbara Ukropcova, Daniela Gasperikova, Thierry Pedrazzini, Wilhelm Krek.  '''Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system'''.  ''Genes Dev'', 2012; DOI: 10.1101/gad.180406.111.</ref> In mice undergoing calorie restriction, SIRT2 levels increase in white fat tissue and kidneys.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Fei Wang, Margaret Nguyen, F. Xiao-Feng Qin, Qiang Tong.  '''SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction'''.  ''Aging Cell'', 2007; 6: 505-514.</ref>

@@ Line 173: / Line 173: @@
 ==Dietary activators of sirtuins==
-Dietary ingredients, functional foods, and nutraceuticals provide great hope for promoting health span and longevity, along with preventing age-related diseases <ref>CKB Ferrari.  '''Functional foods, herbs an nutraceuticals: towards biochemical mechanisms of healthy aging'''.  ''Biogerontology'', 2004; 5: 275-289.
+Dietary ingredients, functional foods, and nutraceuticals provide great hope for promoting health span and longevity, along with preventing age-related diseases.<ref>CKB Ferrari.  '''Functional foods, herbs an nutraceuticals: towards biochemical mechanisms of healthy aging'''.  ''Biogerontology'', 2004; 5: 275-289.
-Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref>.  Sirtuin-activating compounds derived from plants include flavones, stilbenes, chalcones, and anthocyanidins, which can directly activate SIRT1 <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref>.  Other agents reported to have anti-aging effects through modulating the SIRT1 cellular pathway include resveratrol <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Sirtuin-activating compounds derived from plants include flavones, stilbenes, chalcones, and anthocyanidins can directly activate SIRT1.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Other agents reported to have anti-aging effects through modulating the SIRT1 cellular pathway include resveratrol,<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-Chung-Lan Kao, Liang-Kung Chen, Yuh-Lih Chang, Ming-Chih Yung, Chuan-Chih Hsu, Yu-Chih Chen, Wen-Liang Lo, Shih-Jen Chen, Hung-Hai Ku, Shin-Jang Hwang.  '''Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation'''.  ''J Atheroscler Thromb'', 2010; 17: 970-979.</ref>, cilostazol <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Chung-Lan Kao, Liang-Kung Chen, Yuh-Lih Chang, Ming-Chih Yung, Chuan-Chih Hsu, Yu-Chih Chen, Wen-Liang Lo, Shih-Jen Chen, Hung-Hai Ku, Shin-Jang Hwang.  '''Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation'''.  ''J Atheroscler Thromb'', 2010; 17: 970-979.</ref> cilostazol,<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-Hidetaka Ota, Masato Eto, Mitsunobu R. Kano, Sumito Ogawa, Katsuya Iijima, Masahiro Akishita, Yasuyoshi Ouchi.  '''Cilostazol inhibits oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells'''.  ''Arterioscler Thromb Vasc Biol'', 2008; 28: 1634-1639.</ref>, paeonol <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Hidetaka Ota, Masato Eto, Mitsunobu R. Kano, Sumito Ogawa, Katsuya Iijima, Masahiro Akishita, Yasuyoshi Ouchi.  '''Cilostazol inhibits oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells'''.  ''Arterioscler Thromb Vasc Biol'', 2008; 28: 1634-1639.</ref> paeonol,<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-Juliana Jamal, Mohd Rais Mustafa, Pooi-Fong Wong.  '''Paeonol protects against premature senescence in endothelial cells by modulating Sirtuin 1 pathway'''.  ''J Ethnopharmacol'', 2014; 154: 428-436.</ref>, statins <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Juliana Jamal, Mohd Rais Mustafa, Pooi-Fong Wong.  '''Paeonol protects against premature senescence in endothelial cells by modulating Sirtuin 1 pathway'''.  ''J Ethnopharmacol'', 2014; 154: 428-436.</ref> statins,<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-Hidetaka Ota, Masato Eto, Mitsunobu R. Kano, Tomoaki Kahyo, Mitsutoshi Setou, Sumito Ogawa, Katsuya Iijima, Masahiro Akishita, Yasuyoshi Ouchi.  '''Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway'''.  ''Arterioscler Thromb Vasc Biol'', 2010; 30: 2205-2211.</ref>, hydrogen sulfide <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Hidetaka Ota, Masato Eto, Mitsunobu R. Kano, Tomoaki Kahyo, Mitsutoshi Setou, Sumito Ogawa, Katsuya Iijima, Masahiro Akishita, Yasuyoshi Ouchi.  '''Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway'''.  ''Arterioscler Thromb Vasc Biol'', 2010; 30: 2205-2211.</ref> hydrogen sulfide,<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
@@ Line 194: / Line 194: @@
-Meihua Zheng, Weili Qiao, Jie Cui, Lei Liu, Hong Liu, Zhirong Wang, Changdong Yan.  '''Hydrogen sulfide delays nicotinamide-induced premature senescence via upregulation of SIRT1 in human umbilical vein endothelial cells'''.  ''Mol Cell Biochem'', 2014; DOI: 10.1007/s11010-014-2046-y.</ref> and persimmon <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Meihua Zheng, Weili Qiao, Jie Cui, Lei Liu, Hong Liu, Zhirong Wang, Changdong Yan.  '''Hydrogen sulfide delays nicotinamide-induced premature senescence via upregulation of SIRT1 in human umbilical vein endothelial cells'''.  ''Mol Cell Biochem'', 2014; DOI: 10.1007/s11010-014-2046-y.</ref> and persimmon.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-Young A. Lee, Eun Ju Cho, Takako Yokozawa.  '''Protective effect of persimmon (''Diospyros kaki'') peel proanthocyanidin against oxidative damage under H2O2-induced cellular senescence'''.  ''Biol Pharm Bull'', 2008; 31: 1265-1269.</ref>.  Polyphenols, including curcumin, can also modulate sirtuins <ref>Sangwoon Chung, Hongwei Yao, Samuel Caito, Jae-woong Hwang, Gnanapragasam Arunachalam, Irfan Rahman.  '''Regulation of SIRT1 in cellular functions: role of polyphenols'''.  ''Arch Biochem Biophys'', 2010; DOI: 10.1016/j.abb.2010.05.003.
+Young A. Lee, Eun Ju Cho, Takako Yokozawa.  '''Protective effect of persimmon (''Diospyros kaki'') peel proanthocyanidin against oxidative damage under H2O2-induced cellular senescence'''.  ''Biol Pharm Bull'', 2008; 31: 1265-1269.</ref> Polyphenols, including curcumin, can also modulate sirtuins.<ref>Sangwoon Chung, Hongwei Yao, Samuel Caito, Jae-woong Hwang, Gnanapragasam Arunachalam, Irfan Rahman.  '''Regulation of SIRT1 in cellular functions: role of polyphenols'''.  ''Arch Biochem Biophys'', 2010; DOI: 10.1016/j.abb.2010.05.003.
@@ Line 203: / Line 203: @@
-T. Jayasena, A. Poljak, G. Smythe, N. Braidy, G. Munch, P. Sachdev.  '''The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease'''.  ''Ageing Res Rev'', 2013; DOI: 10.1016/j.arr.2013.06.003.</ref>.  The most well-described and recognized natural compound stimulating SIRT1 is resveratrol.  Activating SIRT1 with resveratrol supplementation increases lifespan and improves healthspan of several species <ref>Joseph A. Baur, Kevin J. Pearson, Nathan L. Price, Hamish A. Jamieson, Carles Lerin, Avash Kalra, Vinayakumar V. Prabhu, Joanne S. Allard, Buillermo Lepez-Lluch, Kaitlyn Lewis, Paul J. Pistell, Suresh Poosala, Kevin G. Becker, Olivier Boss, Dana Gwinn, Mingyi Wang, Sharan Ramaswamy, Kenneth W. Fishbein, Richard G. Spencer, Edward G. Lakatta, David Le Couteur, Reuben J. Shaw, Placido Navas, Pere Puigserver, Donald K. Ingram, Rafael de Cabo, David A. Sinclair.  '''Resveratrol improves health and survival of mice on a high-calorie diet'''.  ''Nature'', 2006; DOI: 10.1038/nature05354.
+T. Jayasena, A. Poljak, G. Smythe, N. Braidy, G. Munch, P. Sachdev.  '''The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease'''.  ''Ageing Res Rev'', 2013; DOI: 10.1016/j.arr.2013.06.003.</ref> The most well-described and recognized natural compound stimulating SIRT1 is resveratrol. Activating SIRT1 with resveratrol supplementation increases lifespan and improves healthspan of several species.<ref>Joseph A. Baur, Kevin J. Pearson, Nathan L. Price, Hamish A. Jamieson, Carles Lerin, Avash Kalra, Vinayakumar V. Prabhu, Joanne S. Allard, Buillermo Lepez-Lluch, Kaitlyn Lewis, Paul J. Pistell, Suresh Poosala, Kevin G. Becker, Olivier Boss, Dana Gwinn, Mingyi Wang, Sharan Ramaswamy, Kenneth W. Fishbein, Richard G. Spencer, Edward G. Lakatta, David Le Couteur, Reuben J. Shaw, Placido Navas, Pere Puigserver, Donald K. Ingram, Rafael de Cabo, David A. Sinclair.  '''Resveratrol improves health and survival of mice on a high-calorie diet'''.  ''Nature'', 2006; DOI: 10.1038/nature05354.
@@ Line 209: / Line 209: @@
-Laurent Mouchiroud, Laurent Molin, Nicolas Dalliere, Florence Solari.  '''Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging'''.  ''BioFactors'', 2010; DOI: 10.1002/biof.127.</ref>.  Natural anti-aging compounds also include quercetin, butein, fisetin, kaempferol, catechins, and proanthocyanidins <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Laurent Mouchiroud, Laurent Molin, Nicolas Dalliere, Florence Solari.  '''Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging'''.  ''BioFactors'', 2010; DOI: 10.1002/biof.127.</ref> Natural anti-aging compounds also include quercetin, butein, fisetin, kaempferol, catechins, and proanthocyanidins.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-T. Jayasena, A. Poljak, G. Smythe, N. Braidy, G. Munch, P. Sachdev.  '''The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease'''.  ''Ageing Res Rev'', 2013; DOI: 10.1016/j.arr.2013.06.003.</ref>.  Some Traditional Chinese Medicines have natural compounds with potent SIRT1-activating effects <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+T. Jayasena, A. Poljak, G. Smythe, N. Braidy, G. Munch, P. Sachdev.  '''The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease'''.  ''Ageing Res Rev'', 2013; DOI: 10.1016/j.arr.2013.06.003.</ref> Some traditional Chinese medicines have natural compounds with potent SIRT1-activating effects.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
-Yi Wang, Xxinying Liang, Yaqi Chen, Xiaoping Zhao.  '''Screening SIRT1 activators from medicinal plants as bioactive compounds against oxidative damage in mitochondrial function'''.  ''Oxid Med Cell Longev'', 2016; DOI: 10.1155/2016/4206392.</ref>.  Activating sirtuins through the regulation of NAD+ levels offers an alternative method of stimulating sirtuin function.
+Yi Wang, Xxinying Liang, Yaqi Chen, Xiaoping Zhao.  '''Screening SIRT1 activators from medicinal plants as bioactive compounds against oxidative damage in mitochondrial function'''.  ''Oxid Med Cell Longev'', 2016; DOI: 10.1155/2016/4206392.</ref> Activating sirtuins through the regulation of NAD+ levels offers an alternative method of stimulating sirtuin function.
-Functional food is a promising method for anti-aging interventions.  Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging.
+Functional food is a promising method for anti-aging interventions. Modulating SIRT1 function through consumption of these foods and dietary ingredients could represent a new way of counteracting the effects of aging.
 ==Further reading==

@@ Line 86: / Line 86: @@
 ==Research==
 ===Aging===
-Research on aging indicates sirtuins are essential factors for delaying cell deterioration with age, cellular senescence.  Scientists consider cellular senescence as a beneficial process to inhibit the accumulation of abnormal cells in young organisms.  Stress causes this accumulation.  Such an accumulation of abnormal cells is detrimental to older organisms and thought to induce age-related diseases.  Additionally, senescent cells increase with aging <refr>(Krtolica and Campisi, 2002; Lee et al., 2019)<nowiki></ref></nowiki>.
+Research on aging indicates sirtuins are essential factors for delaying cell cellular senescence, deterioration with age. Scientists consider cellular senescence as a beneficial process to inhibit the accumulation of abnormal cells in young organisms caused by stress. Such accumulation of abnormal cells is detrimental to older organisms and thought to induce age-related diseases. Additionally, senescent cells increase with aging <refr>(Krtolica and Campisi, 2002; Lee et al., 2019)<nowiki></ref></nowiki>.
-Two Sirtuins have been investigated in mammals with protective effects from senescence in mammals, SIRT1 and SIRT6.  Levels of these two Sirtuins are reported to decrease in senescent cell lines of mice <ref>Tarique Anwar, Sanjeev Khosla, Gayatri Ramakrishna.  '''Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status'''.  ''Cell Cycle'', 2016; DOI: 10.1080/15384101.2016.1189041.
+Two sirtuins have been investigated in mammals with protective effects from senescence, SIRT1 and SIRT6. Levels of these two irtuins are reported to decrease in senescent cell lines of mice.<ref>Tarique Anwar, Sanjeev Khosla, Gayatri Ramakrishna.  '''Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status'''.  ''Cell Cycle'', 2016; DOI: 10.1080/15384101.2016.1189041.
@@ Line 100: / Line 100: @@
-Myung Jin Son, Youjeong Kwon, Tawkwon Son, Yee Sook Cho.  '''Restoration of mitochondrial NAD+ levels delays stem cell senescence and facilitates reprogramming of aged somatic cells'''.  ''Stem Cells'', 2016; DOI: 10.1002/stem.2460.</ref>.  Reducing SIRT1 and SIRT6 using molecular inhibitors of their function, siRNA or miRNA, promotes early senescence characteristics in the interior of blood vessels, endothelial cells <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
+Myung Jin Son, Youjeong Kwon, Tawkwon Son, Yee Sook Cho.  '''Restoration of mitochondrial NAD+ levels delays stem cell senescence and facilitates reprogramming of aged somatic cells'''.  ''Stem Cells'', 2016; DOI: 10.1002/stem.2460.</ref> Reducing SIRT1 and SIRT6's function using molecular inhibitors, siRNA or miRNA, promotes early senescence characteristics in endothelial cells located at the interior of blood vessels.<ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
@@ Line 109: / Line 109: @@
-Hidetaka Ota, Masahiro Akishita, Masato Eto, Katsuya Iijima, Masao Kaneki, Yasuyoshi Ouchi.  '''Sirt1 modulates premature senescence-like phenotype in human endothelial cells'''.  ''J Mol Cell Cardiol'', 2007; DOI: 101016/j.yjmcc.2007.08.008.</ref>.  Increasing SIRT1 and SIRT6 gene expression through over-expression suppresses cellular senescence <ref>Jian Chen, Jun-Jun Xie, Meng-Yun Jin, Yun-Tao Gu, Cong-Cong Wu, Wei-Jun Guo, Ying-Zhao Yan, Zeng-Jie Zhang, Jian-Le Wang, Xiao-Lei Zhang, Yan Lin, Jia-Li Sun, Guang-Hui Zhu, Xiang-Yang Wang, Yao-Sen Wu. '''Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration'''.  ''Cell Death Dis'', 2018; DOI: 10.1038/s41419-017-0085-5.
+Hidetaka Ota, Masahiro Akishita, Masato Eto, Katsuya Iijima, Masao Kaneki, Yasuyoshi Ouchi.  '''Sirt1 modulates premature senescence-like phenotype in human endothelial cells'''.  ''J Mol Cell Cardiol'', 2007; DOI: 101016/j.yjmcc.2007.08.008.</ref> Increasing SIRT1 and SIRT6 gene expression through over-expression suppresses cellular senescence.<ref>Jian Chen, Jun-Jun Xie, Meng-Yun Jin, Yun-Tao Gu, Cong-Cong Wu, Wei-Jun Guo, Ying-Zhao Yan, Zeng-Jie Zhang, Jian-Le Wang, Xiao-Lei Zhang, Yan Lin, Jia-Li Sun, Guang-Hui Zhu, Xiang-Yang Wang, Yao-Sen Wu. '''Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration'''.  ''Cell Death Dis'', 2018; DOI: 10.1038/s41419-017-0085-5.
@@ Line 121: / Line 121: @@
-Yi Zu, Ling Liu, Mary Y.K. Lee, Cheng Xu, Yan Liang, Ricky Y. Man, Paul M. Vanhoutte, Yu Wang.  '''SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells'''.  ''Circ Res'', 2010; DOI: 10.1161/CIRCRESAHA.109.215483.</ref>.  Altogether, this research indicates Sirtuins play significant roles in cellular senescence.
+Yi Zu, Ling Liu, Mary Y.K. Lee, Cheng Xu, Yan Liang, Ricky Y. Man, Paul M. Vanhoutte, Yu Wang.  '''SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells'''.  ''Circ Res'', 2010; DOI: 10.1161/CIRCRESAHA.109.215483.</ref> Altogether, research indicates sirtuins play significant roles in cellular aging.
-Suppression of cellular senescence with Sirtuins stems from preventing telomere degradation and promoting DNA damage repair, two key processes in maintaining DNA integrity.  For example, SIRT1 and SIRT6 have known roles in regulating telomere reverse transcriptase expression, an enzyme necessary for telomere elongation <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
+Suppression of age-caused cellular deterioration with sirtuins stems from two key processes in maintaining DNA integrity -- preventing telomere degradation and promoting DNA damage repair. Telomeres are protective caps that sit on the end of the DNA strands but these caps shorten and fray as cellular senescence occur as one age. Telomere elongation is necessary to avoid premature cellular senescence. SIRT1 and SIRT6 have known roles in regulating telomere reverse transcriptase expression, an enzyme necessary for telomere elongation.<ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
-Shuntaro Yamashita, Kaori Ogawa, Takahiro Ikei, Miyako Udono, Tsukasa Fujiki, Yoshinori Katakura.  '''SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene'''.  ''Biochem Biophys Res Commun'', 2012; DOI: 10.1016/j.bbrc.2011.12.021.</ref>.  Telomere elongation is necessary to avoid premature cellular senescence.  SIRT1 and SIRT6 also remove acetyl groups, deacetylate, from proteins called ‘histones.’  DNA wraps around ‘histones,’ a process necessary for DNA stability.  Through deacetylating histones, histone 3 lysine 9 and histone 3 lysine 56, integrity of telomeres increases along with general DNA integrity <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
+Shuntaro Yamashita, Kaori Ogawa, Takahiro Ikei, Miyako Udono, Tsukasa Fujiki, Yoshinori Katakura.  '''SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene'''.  ''Biochem Biophys Res Commun'', 2012; DOI: 10.1016/j.bbrc.2011.12.021.</ref> SIRT1 and SIRT6 also remove acetyl groups from proteins called histones, the mechanism is also known as deacetylation. DNA wraps around histones for DNA stability. Through deacetylating histones at histone 3 lysine 9 and histone 3 lysine 56, the integrity of telomeres increases along with general DNA integrity.<ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
-Mateusz Watroba, Ilona Dudek, Marta Skoda, Aleksandra Stangret, Przemyslaw Rzodkiewicz, Dariusz Szukiewicz.  '''Sirtuins, epigenetics and longevity'''.  ''Ageing Res Rev'', 2017; DdOI: 10.1016/j.arr.2017.08.001.</ref>.  Additionally, research indicates SIRT1 and SIRT6 are recruited to damaged DNA sites.  SIRT1 and SIRT6 then promote DNA repair through deacetylation of repair proteins such as poly (ADP-ribose) polymerase (PARP)-1, Ku70, NBS, and Werner (WRN) helicase <ref>Jaemin Jeong, Kyungmi Juhn, Hansoo Lee, Sang-Hoon Kim, Bon-Hong Min, Kyung-Mi Lee, Myung-Haeng Cho, Gil-Hong Park, Kee-Ho Lee.  '''SIRT1 promotes DNA repair activity and deacetylation of Ku70'''.  ''Exp Mol Med'', 2007; DOI: 10.1038/emm.2007.2.
+Mateusz Watroba, Ilona Dudek, Marta Skoda, Aleksandra Stangret, Przemyslaw Rzodkiewicz, Dariusz Szukiewicz.  '''Sirtuins, epigenetics and longevity'''.  ''Ageing Res Rev'', 2017; DdOI: 10.1016/j.arr.2017.08.001.</ref> Additionally, research indicates SIRT1 and SIRT6 are recruited to damaged DNA sites. The proteins then promote DNA repair through deacetylating repair proteins such as poly (ADP-ribose) polymerase (PARP)-1, Ku70, NBS, and Werner (WRN) helicase <ref>Jaemin Jeong, Kyungmi Juhn, Hansoo Lee, Sang-Hoon Kim, Bon-Hong Min, Kyung-Mi Lee, Myung-Haeng Cho, Gil-Hong Park, Kee-Ho Lee.  '''SIRT1 promotes DNA repair activity and deacetylation of Ku70'''.  ''Exp Mol Med'', 2007; DOI: 10.1038/emm.2007.2.
@@ Line 143: / Line 143: @@
 Zhigang Yuan, Edward Seto.  '''A functional link between SIRT1 deacetylase and NBS1 in DNA damage response'''.  ''Cell Cycle'', 2007; DOI: 10.4161/cc.6.23.5026.</ref>.
-In addition to roles in maintaining DNA integrity and repairing damaged sites of DNA thus preventing cellular senescence, research indicates Sirtuins regulate lifespan in several animals.  Increased levels of the Sirtuin gene, SIR2, in yeast extends its lifespan.  The same gene in other animals, homologues, extends lifespan in roundworms, fruit flies, and mice, also <ref>Matt Kaeberlein, Mitch McVey, Leonard Guarente.  '''The ''SIR2/3/4'' complex and ''SIR2'' alone promote longevity in ''Saccharomyces cerevisiae'' by two different mechanisms'''.  ''Genes Dev'', 1999; DOI: 10.1101/gad.13.19.2570.
+In addition to roles in maintaining DNA integrity and repairing damaged sites of DNA to preventing cellular senescence, sirtuins regulate lifespan in several animals. Increased levels of the sirtuin gene, SIR2, in yeast extends its lifespan. The equivalent gene in found in other animals such as roundworms, fruit flies, and mice, also extends their lifespan.<ref>Matt Kaeberlein, Mitch McVey, Leonard Guarente.  '''The ''SIR2/3/4'' complex and ''SIR2'' alone promote longevity in ''Saccharomyces cerevisiae'' by two different mechanisms'''.  ''Genes Dev'', 1999; DOI: 10.1101/gad.13.19.2570.
@@ Line 155: / Line 155: @@
-Heidi A. Tissenbaum, Leonard Guarente.  '''Increased dosage of a ''sir-2'' gene extends lifespan in ''Caenorhabditis elegans'''''.  ''Nature'', 2001; DOI: 10.1038/35065638.</ref>.  The first study of the longevity enhancing effects of SIR2 occurred approximately 20 years ago in yeast <ref>Matt Kaeberlein, Mitch McVey, Leonard Guarente.  '''The ''SIR2/3/4'' complex and ''SIR2'' alone promote longevity in ''Saccharomyces cerevisiae'' by two different mechanisms'''.  ''Genes Dev'', 1999; DOI: 10.1101/gad.13.19.2570.
+Heidi A. Tissenbaum, Leonard Guarente.  '''Increased dosage of a ''sir-2'' gene extends lifespan in ''Caenorhabditis elegans'''''.  ''Nature'', 2001; DOI: 10.1038/35065638.</ref> The first study of the longevity enhancing effects of SIR2 occurred approximately 20 years ago in yeast.<ref>Matt Kaeberlein, Mitch McVey, Leonard Guarente.  '''The ''SIR2/3/4'' complex and ''SIR2'' alone promote longevity in ''Saccharomyces cerevisiae'' by two different mechanisms'''.  ''Genes Dev'', 1999; DOI: 10.1101/gad.13.19.2570.
-Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.</ref>.  Follow-up investigations examined effects of increasing expression of Sir2 in other organisms.  For example, increasing sir2.1 expression levels 7-fold in roundworms extended the lifespan of the worms by 14.8-50.5% <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
+Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.</ref> Follow-up investigations examined effects of Sir2 enhancement in other organisms.  Increasing sir2.1expression levels by 7-fold in roundworms extended the lifespan of the worms by 14.8-50.5%. <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
-Heidi A. Tissenbaum, Leonard Guarente.  '''Increased dosage of a ''sir-2'' gene extends lifespan in ''Caenorhabditis elegans'''''.  ''Nature'', 2001; DOI: 10.1038/35065638.</ref>.  Furthermore, a mutation resulting in reduced expression of the sir2.1 gene resulted in decreased lifespan of roundworms.  In fruit flies, inducing increased expression, over-expressing, the dSir2 gene in neuronal cells or fat cells extended lifespan approximately 52% and 32.2%, respectively <ref>Kushal Kr. Banerjee, Champakali Ayyub, Syed Zeeshan Ali, Vinesh Mandot, Nagaraj G. Prasad, Ullas Kolthur-Seetharam.  '''dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner'''.  ''Cell Rep'', 2012; DOI: 10.1016/j.celrep.2012.11.013.
+Heidi A. Tissenbaum, Leonard Guarente.  '''Increased dosage of a ''sir-2'' gene extends lifespan in ''Caenorhabditis elegans'''''.  ''Nature'', 2001; DOI: 10.1038/35065638.</ref> Furthermore, a mutation resulting in reduced expression of the sir2.1 gene resulted in decreased lifespan of roundworms. In fruit flies, inducing over expressing the dSir2 gene in neuronal cells or fat cells extended lifespan approximately by 52% and 32.2%, respectively. <ref>Kushal Kr. Banerjee, Champakali Ayyub, Syed Zeeshan Ali, Vinesh Mandot, Nagaraj G. Prasad, Ullas Kolthur-Seetharam.  '''dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner'''.  ''Cell Rep'', 2012; DOI: 10.1016/j.celrep.2012.11.013.
@@ Line 167: / Line 167: @@
-Blanka Rogina, Stephen L. Helfand.  '''Sir2 mediates longevity in the fly through a pathway related to calorie restriction'''.  ''Proc Natl Acad Sci U S A'', 2004; DOI: 10.1073/pnas.0404184101.</ref>.  Mice over-expressing SIRT1 in the brain, the hypothalamus more specifically, had an increased median lifespan of 16% in females and 9% in males <ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
+Blanka Rogina, Stephen L. Helfand.  '''Sir2 mediates longevity in the fly through a pathway related to calorie restriction'''.  ''Proc Natl Acad Sci U S A'', 2004; DOI: 10.1073/pnas.0404184101.</ref> Mice over-expressing SIRT1 in the brain, more specifically in the hypothalamus, had an increased median lifespan of 16% in females and 9% in males.<ref>Shin-Hae Lee, Ji-Hyeon Lee, Hye-Yeon Lee, Kyung-Jin Min.  '''Sirtuin signaling in cellular senescence and aging'''.  ''BMB Rep'', 2019; DOI: 10.5483/BMBRep.2019.52.1.290.
-Akiko Satoh, Cynthia S. Brace, Nick Rensing, Paul Clifton, David F. Wozniak, Erik D. Herzog, Kelvin A. Yamada, Shin-ichiro Imai.  '''Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH'''.  ''Cell Metab'', 2013; DOI: 10.1016/j.cmet.2013.07.013.</ref>.
+Akiko Satoh, Cynthia S. Brace, Nick Rensing, Paul Clifton, David F. Wozniak, Erik D. Herzog, Kelvin A. Yamada, Shin-ichiro Imai.  '''Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH'''.  ''Cell Metab'', 2013; DOI: 10.1016/j.cmet.2013.07.013.</ref>
 ==Dietary activators of sirtuins==

@@ Line 15: / Line 15: @@
 ==Functions of sirtuins in mammals==
-The functions of sirtuins play key roles in metabolism, inflammation, DNA repair, insulin secretion, and aging.  In general, through removing these molecular tags, sirtuins suppress DNA expression and promote chromosome stability.
+The functions of sirtuins play key roles in metabolism, inflammation, DNA repair, insulin secretion, and aging. In general, through removing these molecular tags, sirtuins suppress DNA expression, promote chromosome stability and regulate cellular health.
 ==Types of sirtuins in mammals==
@@ Line 69: / Line 69: @@
 :''Main article: [[SIRT1]]''
-SIRT1, the most studied of the sirtuins in this family of proteins,could play an important role in aging.  Mice with an extra copy of the SIRT1 gene, which have higher levels of SIRT1 in cells, have lower levels of DNA damage.  These mice also have lower levels of a protein, p16, which is a marker of aging <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+SIRT1, the most studied of the sirtuins family, could play an important role in aging. Mice with an extra copy of the SIRT1 gene produces higher levels of SIRT1 proteins in cells, resulting in lower levels of DNA damage. These mice also have lower levels of "p16," a protein that serves as a marker of aging.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Daniel Herranz, Marta Canamero, Francisca Mulero, Barbara Martinez-Pastor, Oscar Fernandez-Capetillo, Manuel Serrano.  '''Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer syndrome'''.  ''Nat Commun'', 2010; DOI: 10.1038/ncomms1001.</ref> SIRT1 suppresses the activity of genes associated with aging. However, the levels of the protein drops in cells as organisms age, reactivating the aging-related genes.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Jaw-woong Hwang, Hongwei Yao, Samuel Caito, Isaac K. Sundar, Irfan Rahman.  '''Redox regulation of SIRT1 in inflammation and cellular senescence'''.  ''Free Radic Biol Med'', 2013; DOI: 10.1016/j.freerradbiomed.2013.03.015.</ref> SIRT1 levels also decrease with age in liver cells, mostly due to lower NAD+ availability.<ref>Nady Braidy, Gilles J. Guillemin, Hussein Mansour, Tailoi Chan-Ling, Anne Poljak, Ross Grant.  '''Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats'''.  ''PLoS One'', 2011; DOI: 10.1371/journal.pone.0019194.</ref> DNA damage occurs with falling SIRT1 levels.
 ===SIRT2===
-SIRT2 levels may be markers of obesity.  SIRT2 levels drop in fat tissue of obese people <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+SIRT2 levels may be a marker of obesity. In obese individuals, the levels of the protein drops in fat tissue.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Jaya Krishnan, Carsten Danzer, Tatiana Simka, Josef Ukropec, Katharina Manuela Walter, Susann Kumpf, Peter Mirtschink, Barbara Ukropcova, Daniela Gasperikova, Thierry Pedrazzini, Wilhelm Krek.  '''Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system'''.  ''Genes Dev'', 2012; DOI: 10.1101/gad.180406.111.</ref> In mice undergoing calorie restriction, SIRT2 levels increase in white fat tissue and kidneys.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Fei Wang, Margaret Nguyen, F. Xiao-Feng Qin, Qiang Tong.  '''SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction'''.  ''Aging Cell'', 2007; 6: 505-514.</ref>
 ===SIRT3===
-Evidence exists SIRT3 influences longevity in humans <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref>.  A particular gene marker in the SIRT3 gene, a polymorphism, is found more often in people who live longer <ref>D. Bellizzi, S. Dato, P. Cavalcante, G. Covello, F. Di Cianni, G. Passarino, G. Rose, G. De Benedictis.  '''Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13'''.  ''Genomics'', 2007; 89(1): 143-150.
+Evidence suggests that SIRT3 plays a role in human longevity.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> A particular gene marker in the SIRT3 gene, a polymorphism, is found more often in people who live longer.<ref>D. Bellizzi, S. Dato, P. Cavalcante, G. Covello, F. Di Cianni, G. Passarino, G. Rose, G. De Benedictis.  '''Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13'''.  ''Genomics'', 2007; 89(1): 143-150. Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Mice lacking SIRT3 have decreased oxygen consumption and increased markers of cellular stress, reactive oxygen species.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Enxuan Jing, Brice Emanuelli, Matthew D. Hirschey, Jeremie Boucher, Kevin Y. Lee, David Lombard, Eric M. Verdin, C. Ronald Kahn.  '''Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production'''.  ''Proc Natl Acad Sci U S A'', 2011; DOI: 10.1073/pnas.1111308108.</ref>
 ===SIRT6===
-Research using mice lacking SIRT6 provide the first evidence sirtuins are involved in regulating mammalian aging.  With reduced levels of SIRT6, mice fail to reach a normal lifespan <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref>.  Three weeks after birth, these mice exhibit premature aging and degeneration, which results in death around the fourth week of life <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref>.  Mice without SIRT6 are also smaller than ‘normal,’ wild type, individuals.
+Research using mice lacking SIRT6 provide the first evidence that sirtuins are involved in regulating mammalian aging. With reduced levels of SIRT6, mice fail to reach a normal lifespan.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Three weeks after birth, these mice exhibit premature aging and degeneration, which results in death around the fourth week of life.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.</ref> Mice without SIRT6 are also smaller than ‘normal’ individuals.
 ===SIRT7===
-Mice lacking SIRT7 age prematurely and have heart complications, lethal heart hypertrophy <ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9.
+Mice lacking SIRT7 age prematurely and have heart complications, lethal heart hypertrophy.<ref>Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska.  '''Sirtuins, a promising target in slowing down the ageing process'''.  ''Biogerontology'', 2017; DOI: 10.1007/s10522-017-9685-9. Olesya Vakhrusheva, Christian Smolka, Praveen Gajawada, Sawa Kostin, Thomas Boettger, Thomas Kubin, Thomas Braun, Eva Bober.  '''Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice'''.  ''Circ Res'', 2008; 102(6): 703-710.</ref>
 ==Research==