Molecular Mechanisms of Cardiovascular Aging
Abstract
BACKGROUND: The average lifespan of humans is increasing, and with it the percentage of people entering the 65 and older age group is growing rapidly and will continue to do so in the next 20 years. Within this age group, cardiovascular disease will remain the leading cause of death, and the cost associated with treatment will continue to increase. Aging is an inevitable part of life and unfortunately poses the largest risk factor for cardiovascular disease.
CONTENT: We provide an overview of some of the molecular mechanisms involved in regulating lifespan and health, including mitochondria, telomeres, stem cells, sirtuins, Adenosine Monophosphate-activated Protein Kinase, Mammalian Target of Rapamycin and Insulin-like Growth Factor 1. We also provide future perspectives of lifespan and health, which are intimately linked fields.
SUMMARY: Aging remains the biggest non-modifiable risk factor for cardiovascular disease. The biological, structural and mechanical changes in senescent cardiovascular system are thought to contribute in increasing incidence of cardiovascular disease in aging. Understanding the mechanisms contributing to such changes is therefore crucial for both prevention and development of treatment for cardiovascular diseases.
KEYWORDS: cardiovascular aging, mitochondria, telomeres, sirtuin, stem cells
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Grayson M. Aging. Nature. 2012; 492: S1, CrossRef.
Offord E, Major G, Vidal K, Gentle-Rapinett G, Batge E, Beck T, et al. Lausanne: Nestle Research Center; [n.y]. Nutrition throughout life: innovation for healthy aging [cited on 2014 Jan 3]. Available from: http://research.nestle.com/.
Burton DG. Cellular senescence, ageing and disease. Age (Dordr). 2009; 31: 1-9, CrossRef.
Sharpless NE, DePinho RA. How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol. 2007; 8: 703-13, CrossRef.
Matsushita H, Chang E, Glassford AJ, Cooke JP, Chiu CP, Tsao PS. eNOS activity is reduced in senescent human endothelial cells: Preservation by hTERT immortalization. Circ Res. 2001; 89: 793-8, CrossRef.
Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation. 2002; 105: 1541-4, CrossRef.
Cannon RO 3rd. Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clin Chem. 1998; 44: 1809-19, PMID.
Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part II: the aging heart in health: links to heart disease. Circulation. 2003; 107: 346-54, CrossRef.
North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. 2012; 110: 1097-108, CrossRef.
Fleg JL, Aronow WS, Frishman WH. Cardiovascular drug therapy in the elderly: benefits and challenges. Nat Rev Cardiol. 2011; 8: 13-28, CrossRef.
Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011; 123: 933-44, CrossRef.
Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part II: the aging heart in health: links to heart disease. Circulation. 2003; 107: 346-54, CrossRef.
Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Aging Res Rev. 2009; 8: 18-30, CrossRef.
Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007; 128: 92-105, CrossRef.
Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, et al. Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev. 2007; 128: 83-91, CrossRef.
Ferrucci L, Ble A, Bandinelli S, Lauretani F, Suthers K, Guralnik JM. A flame burning within. Aging Clin Exp Res. 2004; 16: 240-3, CrossRef.
Ancrile B, Lim KH, Counter CM. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev. 2007; 21: 1714-9, CrossRef.
Badache A, Hynes NE. Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. Cancer Res. 2001; 61: 383-91, PMID.
Desai TR, Leeper NJ, Hynes KL, Gewertz BL. Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway. J Surg Res. 2002; 104: 118-23, CrossRef.
Naugler WE, Karin M. The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008; 14: 109-19, CrossRef.
Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004; 6: 447-58, CrossRef.
Tamm I, Kikuchi T, Cardinale I, Krueger JG. Cell-adhesion-disrupting action of interleukin 6 in human ductal breast carcinoma cells. Proc Natl Acad Sci USA. 1994; 91: 3329-33, CrossRef.
Nagabhushanam V, Solache A, Ting LM, Escaron CJ, Zhang JY, Ernst JD. Innate inhibition of adaptive immunity: mycobacterium tuberculosis-induced IL-6 inhibits macrophage responses to IFNgamma. J Immunol. 2003; 171: 4750-7, CrossRef.
Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, et al. Fat tissue, aging, and cellular senescence. Aging Cell. 2010; 9: 667-84, CrossRef.
Coppé JP, Patil CK, Rodier F, Krtolica A, Beauséjour CM, Parrinello S, et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS One. 2010; 5: e9188, CrossRef.
Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, et al. Senescence-associated secretory phenotypes reveal cellnonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008; 6: 2853-68, CrossRef.
Rodier F, Coppé JP, Patil CK, Hoeijmakers WA, Muñoz DP, Raza SR, et al. Persistent DNA damage signaling triggers senescenceassociated inflammatory cytokine secretion. Nat Cell Biol. 2009; 11: 973-9, CrossRef.
Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010; 16: 238-46, CrossRef.
Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013; 123: 966-72, CrossRef.
Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, et al. Heart disease and stroke statistics-2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009; 119: 480-6, CrossRef.
Dai DF, Rabinovich PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res. 2012; 110: 1109-24, CrossRef.
Newgard CB, Sharpless NE. Coming of age: molecular drivers of aging and therapeutic opportunities. J Clin Invest. 2013; 123: 946-50, CrossRef.
Judge S, Jang YM, Smith A, Hagen T, Leeuwenburgh C. Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J. 2005; 19: 419-21, CrossRef.
Ungvari ZI, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith KE, et al. Increased mitochondrial H2O2 production promotes endothelial NF-kappaB activation in aged rat arteries. Am J Physiol Heart Circ Physiol. 2007; 293: H37-47, CrossRef.
Mammucari C, Rizzuto R. Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev. 2010; 131: 536-43, CrossRef.
Trifunovic A, Larsson NG. Mitochondrial dysfunction as a cause of ageing. J Intern Med. 2008; 263: 167-8, CrossRef.
Terzioglu M, Larsson NG. Mitochondrial dysfunction in mammalian ageing. Novartis Found Symp. 2007; 287: 197-213, CrossRef.
Erusalimsky JD. Vascular endothelial senescence: From mechanisms to pathophysiology. J Appl Physiol. 2009; 106: 326-32, CrossRef.
Phaneuf S, Leeuwenburgh C. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regul Integr Comp Physiol. 2002; 282: R423-30, CrossRef.
Csiszar A, Ungvari Z, Koller A, Edwards JG, Kaley G. Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging. Physiol Genomics. 2004; 17: 21-30, CrossRef.
Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008; 8: 157-68, CrossRef.
Anversa P, Li P, Sonnenblick EH, Olivetti G. Effects of aging on quantitative structural properties of coronary vasculature and microvasculature in rats. Am J Physiol. 1994; 267: H1062-73, PMID.
Sonntag WE, Lynch CD, Cooney PT, Hutchins PM. Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology. 1997; 138: 3515-20, CrossRef.
Csiszar A, Labinskyy N, Jimenez R, Pinto JT, Ballabh P, Losonczy G, et al. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev. 2009; 130: 518-27, CrossRef.
van der Loo B, Labugger R, Skepper JN, Bachschmid M, Kilo J, Powell JM, et al. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med. 2000; 192: 1731-44, CrossRef.
Ungvari ZI, Labinskyy N, Gupte S, Chander PN, Edwards JG, Csiszar A. Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. Am J Physiol Heart Circ Physiol. 2008; 294: H2121-8, CrossRef.
Ungvari Z, Bailey-Downs L, Gautam T, Sosnowska D, Wang M, Monticone RE, et al. Age-associated vascular oxidative stress, Nrf2 dysfunction and NF-{kappa}B activation in the non-human primate macaca mulatta. J Gerontol A Biol Sci Med Sci. 2011; 66: 866-75, CrossRef.
Ungvari Z, Bailey-Downs L, Sosnowska D, Gautam T, Koncz P, Losonczy G, et al. Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am J Physiol Heart Circ Physiol. 2011; 301: H363-72, CrossRef.
Ungvari Z, Parrado-Fernandez C, Csiszar A, de Cabo R. Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res. 2008; 102: 519-28, CrossRef.
López-Lluch G, Irusta PM, Navas P, de Cabo R. Mitochondrial biogenesis and healthy aging. Exp Gerontol. 2008; 43: 813-9, CrossRef.
Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004; 6: 463-77, PMID.
Inuzuka Y, Okuda J, Kawashima T, Kato T, Niizuma S, Tamaki Y, et al. Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice. Circulation. 2009; 120: 1695-703, CrossRef.
Taneike M, Yamaguchi O, Nakai A, Hikoso S, Takeda T, Mizote I, et al. Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy. 2010; 6: 600-6, CrossRef.
Tatsuta T, Langer T. Quality control of mitochondria: protection against neurodegeneration and aging. EMBO J. 2008; 27: 306-14, CrossRef.
Wang K, Klionsky DJ. Mitochondria removal by autophagy. Autophagy. 2011; 7: 297-300, CrossRef.
Gottlieb RA, Carreira RS. Autophagy in health and disease. 5. Mitophagy as a way of life. Am J Physiol Cell Physiol. 2010; 299: C203-10, CrossRef.
Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009; 458: 1056-60, CrossRef.
Dutta D, Calvani R, Bernabei R, Leeuwenburgh C, Marzetti E. Contribution of impaired mitochondrial autophagy to cardiac aging. Mechanisms and therapeutic opportunities. Circ Res. 2012; 110: 1125-38, CrossRef.
Burns EM, Kruckeberg TW, Comerford LE, Buschmann MT. Thinning of capillary walls and declining numbers of endothelial mitochondria in the cerebral cortex of the aging primate, macaca nemestrina. J Gerontol. 1979; 34: 642-50, CrossRef.
Burns EM, Kruckeberg TW, Gaetano PK. Changes with age in cerebral capillary morphology. Neurobiol Aging. 1981; 2: 285-91, CrossRef.
Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci. 2010; 65: 1028-41, CrossRef.
Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, et al. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science. 2003; 299: 896-9, CrossRef.
Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem. 2007; 76: 701-22, CrossRef.
Armanios M. Telomeres and age-related disease: how telomere biology informs clinical paradigms. J Clin Invest. 2013; 123: 996-1002, CrossRef.
Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA. 1988; 85: 6622-6, CrossRef.
Allshire RC, Gosden JR, Cross SH, Cranston G, Rout D, Sugawara N, et al. Telomeric repeat from T. thermophile cross hybridizes with human telomeres. Nature. 1988; 332: 656-9, CrossRef.
Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci USA. 1994; 91: 9857-60, CrossRef.
Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008; 42: 301-34, CrossRef.
Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985; 43: 405-13, CrossRef.
Greider CW, Blackburn EH. The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987; 51: 887-98, CrossRef.
Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature. 1989; 337: 331-7, CrossRef.
Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V, Cech TR. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science. 1997; 276: 561-7, CrossRef.
Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, et al. The RNA component of human telomerase. Science. 1995; 269: 1236-41, CrossRef.
d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003; 426: 194-8, CrossRef.
Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010; 464: 520-8, CrossRef.
Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, et al. P53 deficiency rescues the adverse effects of telomere loss cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999; 97: 527-38, CrossRef.
Moleshi J, DePinho RA, Sahin E. Telomeres and mitochondria in the aging heart. Circ Res. 2012; 110: 1226-37, CrossRef.
Sahin E, Colla S, Liesa M, Moslehi J, Müller FL, Guo M, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011; 470: 359-65, CrossRef.
Fuster JJ, Andrés V. Telomere biology and cardiovascular disease. Circ Res. 2006; 99: 1167-80, CrossRef.
Gerhard M, Roddy MA, Creager SJ, Creager MA. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension. 1996; 27: 849-53, CrossRef.
Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, et al. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: Comparison between urban and rural communities in China. Circulation. 1985; 71: 202-10, CrossRef.
Lakatta EG. Cardiovascular aging research: the next horizons. J Am Geriatr Soc. 1999; 47: 613-25, CrossRef.
McGrath BP, Liang YL, Teede H, Shiel LM, Cameron JD, Dart A. Age-related deterioration in arterial structure and function in postmenopausal women: Impact of hormone replacement therapy. Arterioscler Thromb Vasc Biol. 1998; 18: 1149-56, CrossRef.
Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR. Aging, habitual exercise, and dynamic arterial compliance. Circulation. 2000; 102: 1270-5, CrossRef.
Vaitkevicius PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE, et al. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993; 88: 1456-62, CrossRef.
Kitzman DW, Sheikh KH, Beere PA, Philips JL, Higginbotham MB. Age-related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions. J Am Coll Cardiol. 1991; 18: 1243-50, CrossRef.
Port S, Cobb FR, Coleman RE, Jones RH. Effect of age on the response of the left ventricular ejection fraction to exercise. N Engl J Med. 1980; 303: 1133-7, CrossRef.
Dai DF, Rabinovitch PS. Cardiac aging in mice and humans: The role of mitochondrial oxidative stress. Trends Cardiovasc Med. 2009; 19: 213-20, CrossRef.
Antelmi I, de Paula RS, Shinzato AR, Peres CA, Mansur AJ, Grupi CJ. Influence of age, gender, body mass index, and functional capacity on heart rate variability in a cohort of subjects without heart disease. Am J Cardiol. 2004; 93: 381-5, CrossRef.
Fluckiger L, Boivin JM, Quilliot D, Jeandel C, Zannad F. Differential effects of aging on heart rate variability and blood pressure variability. J Gerontol A Biol Sci Med Sci. 1999; 54: B219-24, CrossRef.
Schwartz JB, Gibb WJ, Tran T. Aging effects on heart rate variation. J Gerontol. 1991; 46: M99-106, CrossRef.
Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev. 1993; 73: 413-67, PMID.
Lavu S, Boss O, Elliot PJ, Lambert PD. Sirtuins-novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 2008; 7: 841-53, CrossRef.
Hall JA, Dominy JE, Lee Y, Puigserver P. The sirtuin family’s role in aging and age-associated pathologies. J Clin Invest. 2013; 123: 973-9, CrossRef.
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004; 305: 390-2, CrossRef.
Heilbronn LK, Civitarese AE, Bogacka I, Smith SR, Hulver M, Ravussin E. Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting. Obes Res. 2005; 13: 574-81, CrossRef.
Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science. 2005; 310: 314-7, CrossRef.
Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004; 429: 771-6, CrossRef.
Nemoto S, Fergusson MM, Finkel T. SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem. 2005; 280: 16456-60, CrossRef.
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005; 434: 113-8, CrossRef.
Rasbach KA, Schnellmann RG. Isoflavones promote mitochondrial biogenesis. J Pharmacol Exp Ther. 2008; 325: 536-43, CrossRef.
Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003; 300: 1140-2, CrossRef.
Singh KK. Mitochondrial dysfunction is a common phenotype in aging and cancer. Ann NY Acad Sci. 2004; 1019: 260-4, CrossRef.
Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci USA. 2004; 101: 6659-63, CrossRef.
Hepple RT, Baker DJ, McConkey M, Murynka T, Norris R. Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles. Rejuvenation Res. 2006; 9: 219-22, CrossRef.
Meyer TE, Kovács SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L. Long-term caloric restriction ameliorates the decline in diastolic function in humans. J Am Coll Cardiol. 2006; 47: 398-402, CrossRef.
Minamiyama Y, Bito Y, Takemura S, Takahashi Y, Kodai S, Mizuguchi S, et al. Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats. J Pharmacol Exp Ther. 2007; 320: 535-43, CrossRef.
Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell.. 2006; 126: 941-54, CrossRef.
Liszt G, Ford E, Kurtev M, Guarente L. Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem. 2005; 280: 21313-20, CrossRef.
Landry J, Sutton A, Tafrov ST, Heller RC, Stebbins J, Pillus L, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci USA. 2000; 97: 5807-11, CrossRef.
Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD- dependent histone deacetylase. Nature. 2000; 403: 795-800, CrossRef.
Smith JS, Brachmann CB, Celic I, Kenna MA, Muhammad S, Starai VJ, et al. A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci USA. 2000; 97: 6658-63, CrossRef.
Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, et al. hSIR2 (SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001; 107: 149-59, CrossRef.
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006; 127: 1109-22, CrossRef.
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007; 450: 712-6, CrossRef.
Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Mol Endocrinol. 2007; 21: 1745-55, CrossRef.
Yang T, Fu M, Pestell R, Sauve AA. SIRT1 and endocrine signaling. Trends Endocrinol Metab. 2006; 17: 186-91, CrossRef.
Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007; 28: 91-106, CrossRef.
Freyssenet D. Energy sensing and regulation of gene expression in skeletal muscle. J Appl Physiol. 2007; 102: 529-40, CrossRef.
Delmas D, Jannin B, Latruffe N. Resveratrol: preventing properties against vascular alterations and aging. Mol Nutr Food Res. 2005; 49: 377-95, CrossRef.
Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv. 2006; 6: 36-47, CrossRef.
Labinskyy N, Csiszar A, Veress G, Stef G, Pacher, Oroszi G, et al. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Curr Med Chem. 2006; 13: 989-96, CrossRef.
Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, et al. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 2007; 104: 14855-60, CrossRef.
Novakovic A, Bukarica LG, Kanjuh V, Heinle H. Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol. Basic Clin Pharmacol Toxicol. 2006; 99: 360-4, CrossRef.
Stef G, Csiszar A, Lerea K, Ungvari Z, Veress G. Resveratrol inhibits aggregation of platelets from high-risk cardiac patients with aspirin resistance. J Cardiovasc Pharmacol. 2006; 48: 1-5, CrossRef.
Zbikowska HM, Olas B, Wachowicz B, Krajewski T. Response of blood platelets to resveratrol. Platelets. 1999; 10: 247-52, CrossRef.
Zhang Y, Liu Y, Wang T, Li B, Li H, Wang Z, et al. Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and ionic mechanisms. Biochem Biophys Res Commun. 2006; 340: 1192-9, CrossRef.
Zhou B, Wu LJ, Li LH, Tashiro S, Onodera S, Uchiumi F, et al. Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1. J Pharmacol Sci. 2006; 102: 387-95, CrossRef.
Teisseyre A, Michalak K. Inhibition of the activity of human lymphocyte Kv1.3 potassium channels by resveratrol. J Membr Biol. 2006; 214: 123-9, CrossRef.
Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005; 1: 259-71, CrossRef.
Potente M, Ghaeni L, Baldessari D, Mostoslavsky R, Rossig L, Dequiedt F, et al. SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev. 2007; 21: 2644-58, CrossRef.
Vahtola E, Louhelainen M, Merasto S, Martonen E, Penttinen S, Aahos I, et al. Forkhead class O transcription factor 3a activation and Sirtuin1 overexpression in the hypertrophied myocardium of the diabetic Goto–Kakizaki rat. J Hypertens. 2008; 26: 334-44, CrossRef.
Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J. Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res. 2004; 95: 971-80, CrossRef.
Crow MT. Sir-viving cardiac stress: cardioprotection mediated by a longevity gene. Circ Res. 2004; 95: 953-6, CrossRef.
Hertweck M, Göbel C, Baumeister R. Elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell. 2004; 6: 577-88, CrossRef.
Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, et al. The fork head transcription factor DAF-16 transduces insulinlike metabolic and longevity signals in C. elegans. Nature. 1997; 389: 994-9, CrossRef.
Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: an HNF3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 1997; 278: 1319-22, CrossRef.
Henderson ST, Johnson TE. daf-16 integrates developmental and environmental inputs to mediate aging in the nematode caenorhabditis elegans. Curr Biol. 2001; 11: 1975-80, CrossRef.
Lin K, Hsin H, Libina N, Kenyon C. Regulation of the caenorhabditis elegans longevity protein DAF16 by insulin/IGF-1 and germline signaling. Nat Genet. 2001; 28: 139-45, CrossRef.
Lee SS, Kennedy S, Tolonen AC, Ruvkun G. DAF16 target genes that control C. elegans life-span and metabolism. Science. 2003; 300: 644-7, CrossRef.
Oh SW, Mukhopadhyay A, Dixit BL, Raha T, Green MR, Tissenbaum HA. Identification of direct DAF16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat Genet. 2006; 38: 251-7, CrossRef.
Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, et al. Genes that act downstream of DAF16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003; 424: 277-83, CrossRef.
Salih DA, Brunet A. FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol. 2008; 20: 126-36, CrossRef.
Nakae J, Kitamura T, Silver DL, Kido Y, Biggs WH, Wright CVE, et al. The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest. 2001; 108: 1359-67, CrossRef.
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, et al. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature. 2003; 423: 550-5, CrossRef.
Samuel VT, Choi CS, Phillips TG, Romanelli AJ, Geisler JG, Bhanot S, et al. Targeting Foxo1 in mice using antisense oligonucleotide improves hepatic and peripheral insulin action. Diabetes. 2006; 55: 2042-50, CrossRef.
Nakae J, Biggs WH 3rd, Kitamura T, Cavenee WK, Wright CV, Arden KC, et al. Regulation of insulin action and pancreatic betacell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet. 2002; 32: 245-53, CrossRef.
Nakae J, Kitamura T, Kitamura Y, Biggs WH 3rd, Arden KC, Accili D. The forkhead transcription factor Foxo1 regulates adipocyte differentiation. Dev Cell. 2003; 4: 119-29, CrossRef.
Puig O, Tjian R. Transcriptional feedback control of insulin receptor by dFOXO/FOXO1. Genes Dev. 2005; 19: 2435-46, CrossRef.
Russell SJ, Kahn CR. Endocrine regulation of ageing. Nat Rev Mol Cell Biol. 2007; 8: 681-91, CrossRef.
Oellerich MF, Potente M. FOXOs and sirtuins in vascular growth, maintenance, and aging. Circ Res. 2012; 110: 1238-51, CrossRef.
Fontana L, Partridge L, Longo VD. Extending healthy life span-from yeast to humans. Science. 2010; 328: 321-6, CrossRef.
Castello L, Froio T, Cavallini G, Biasi F, Sapino A, Leonarduzzi G, et al. Calorie restriction protects against age-related rat aorta sclerosis. FASEB J. 2005; 19: 1863-65, CrossRef.
Guo Z, Mitchell-Raymundo F, Yang H, Ikeno Y, Nelson J, Diaz V, et al. Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of apolipoprotein E-deficient mice. Mech Aging Dev. 2002; 123: 1121-31, CrossRef.
Haddad F, Bodell PW, McCue SA, Herrick RE, Baldwin KM. Food restriction-induced transformations in cardiac functional and biochemical properties in rats. J Appl Physiol. 1993; 74: 606-12, PMID.
Seymour EM, Parikh RV, Singer AA, Bolling SF. Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. J Mol Cell Cardiol. 2006; 41: 661-8, CrossRef.
Taffet GE, Pham TT, Hartley CJ. The age-associated alterations in late diastolic function in mice are improved by caloric restriction. J Gerontol A Biol Sci Med Sci. 1997; 52: B285-90, CrossRef.
Mager DE, Wan R, Brown M, Cheng A, Wareski P, Abernethy DR, et al. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J. 2006; 20: 631-7, CrossRef.
Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009; 325: 201-4, CrossRef.
Dolinsky VW, Morton JS, Oka T, Robillard-Frayne I, Bagdan M, Lopaschuk GD, et al. Calorie restriction prevents hypertension and cardiac hypertrophy in the spontaneously hypertensive rat. Hypertension. 2010; 56: 412-21, CrossRef.
Rippe C, Lesniewski L, Connell M, LaRocca T, Donato A, Seals D. Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress. Aging Cell. 2010; 9: 304-12, CrossRef.
Maeda H, Gleiser CA, Masoro EJ, Murata I, McMahan CA, Yu BP. Nutritional influences on aging of fischer 344 rats: II. Pathology. J Gerontol. 1985; 40: 671-88, CrossRef.
Fontana L, Vinciguerra M, Longo VD. Growth factors, nutrient signaling, and cardiovascular aging. Circ Res. 2012; 110: 1139-50, CrossRef.
Speakman JR, Mitchell SE. Caloric restriction. Mol Aspects Med. 2011; 32: 159-221, CrossRef.
Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C, et al. Autophagy regulates aging in C. elegans. Autophagy. 2007; 3: 93-5, CrossRef.
Tóth ML, Sigmond T, Borsos E, Barna J, Erdélyi P, Takács-Vellai K, et al. Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy. 2008; 4: 330-8, CrossRef.
Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, et al. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010; 1: 10, CrossRef.
Fontana L, Klein S. Aging, adiposity, and calorie restriction. JAMA. 2007; 297: 986-94, CrossRef.
Nguyen T, Nioi P, Pickett CB. The nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009; 284: 13291-5, CrossRef.
Kobayashi M, Yamamoto M. Nrf2-keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Adv Enzyme Regul. 2006; 46: 113-40, CrossRef.
Ishii T, Itoh K, Yamamoto M. Roles of nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements. Methods Enzymol. 2002; 348: 182-90, CrossRef.
Zou Y, Jung KJ, Kim JW, Yu BP, Chung HY. Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction. FASEB J. 2004; 18: 320-2, CrossRef.
Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K, Schechtman KB, et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am J Clin Nutr. 2006; 84: 1033-42, PMID.
Guo Z, Mitchell-Raymundo F, Yang H, Ikeno Y, Nelson J, Diaz V, et al. Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of apolipoprotein e-deficient mice. Mech Aging Dev. 2002; 123:1121-31, CrossRef.
Ahmet I, Tae HJ, de Cabo R, Lakatta EG, Talan MI. Effects of calorie restriction on cardioprotection and cardiovascular health. J Mol Cell Cardiol. 2011; 51: 263-71, CrossRef.
Kemi M, Keenan KP, McCoy C, Hoe CM, Soper KA, Ballam GC, et al. The relative protective effects of moderate dietary restriction versus dietary modification on spontaneous cardiomyopathy in male Sprague-Dawley rats. Toxicol Pathol. 2000; 28: 285-96, CrossRef.
Navarro F, Navas P, Burgess JR, Bello RI, De Cabo R, Arroyo A, et al. Vitamin E and selenium deficiency induces expression of the ubiquinone-dependent antioxidant system at the plasma membrane. FASEB J. 1998; 12: 1665-73, PMID.
Navas P, Fernandez-Ayala DM, Martin SF, Lopez-Lluch G, De Caboa R, Rodriguez-Aguilera JC, et al. Ceramide-dependent caspase 3 activation is prevented by coenzyme Q from plasma membrane in serum-deprived cells. Free Radic Res. 2002; 36: 369-74, CrossRef.
Navas P, Villalba JM, de Cabo R. The importance of plasma membrane coenzyme Q in aging and stress responses. Mitochondrion. 2007; 7: S34-40, CrossRef.
Asard H, Berczi A, Caubergs RJ. Plasma Membrane Redox Systems and Their Role in Biological Stress and Disease. Dordrecht: Kluwer; 1998, CrossRef.
Villalba JM, Navarro F, Córdoba F, Serrano A, Arroyo A, Crane FL, et al. Coenzyme Q reductase from liver plasma membrane: purification and role in trans-plasma-membrane electron transport. Proc Natl Acad Sci USA. 1995; 92: 4887-91, CrossRef.
Hyun DH, Emerson SS, Jo DG, Mattson MP, de Cabo R. Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc Natl Acad Sci USA. 2006; 103: 19908-12, CrossRef.
De Cabo R, Cabello R, Rios M, López-Lluch G, Ingram DK, Lane MA, et al. Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver. Exp Gerontol. 2004; 39: 297-304, CrossRef.
Hyun DH, Hunt ND, Emerson SS, Hernandez JO, Mattson MP, de Cabo R. Up-regulation of plasma membrane-associated redox activities in neuronal cells lacking functional mitochondria. J Neurochem. 2007; 100: 1364-74, CrossRef.
López-Lluch G, Rios G, Lane MA, Navas P, de Cabo R. Mouse liver plasma membrane redox system activity is altered by aging and modulated by calorie restriction. Age. 2005; 27: 153-60, CrossRef.
Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, et al. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005; 25: 3032-40, CrossRef.
Zheng J, Mutcherson R 2nd, Helfand SL. Calorie restriction delays lipid oxidative damage in Drosophila melanogaster. Aging Cell. 2005; 4: 209-16, CrossRef.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a highcalorie diet. Nature. 2006; 444: 337-42, CrossRef.
Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008; 8: 157-68, CrossRef.
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009; 460: 392-5, CrossRef.
Dhahbi JM, Mote PL, Fahy GM, Spindler SR. Identification of potential caloric restriction mimetics by microarray profiling. Physiol Genom. 2005; 23: 343-50, CrossRef.
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A pgc1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481: 463-8, CrossRef.
Barger JL, Kayo T, Pugh TD, Prolla TA, Weindruch R. Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart. Exp Gerontol. 2008; 43: 859-66, CrossRef.
DOI: https://doi.org/10.18585/inabj.v5i3.64
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