Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Aging Science
  4. Fast Track Articles
  5. Fast Track Article
image of Nicotinamide Adenine Dinucleotide (NAD)-Dependent Protein Deacetylase, Sirtuin, as a Biomarker of Healthy Life Expectancy: A Mini-Review

Abstract

Although a variety of disease-specific biomarkers have been identified for common lifestyle- or aging-related diseases, there are currently no indices available to measure general health or the existence of pre-symptomatic conditions in various types of tissue and organ damage. A rising body of research suggests that sirtuins may have the potential to be used as an index to assess overall health status and the existence of pre-symptomatic illness states. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD)-dependent deacetylases expressed in a variety of human somatic cells both in health and disease conditions. The activity and expression of SIRTs affect important metabolic pathways, such as cell survival, senescence, proliferation, energy production, stress tolerance, DNA repair, and apoptosis, thereby closely linked to aging and longevity. Given the broad significance of SIRTs in physiological function maintenance, their activity in somatic cells may reflect the early cross-sectional status of tissue damage caused by aging or systemic inflammatory responses that are too early to be detected by disease-specific biomarkers. In this mini-review, we discuss the utility of SIRTs as a surrogate clinical biomarker for health status to evaluate and monitor health life expectancy and the presence of pre-symptomatic illness states.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cas/10.2174/0118746098319674240827104612
2024-10-04
2024-11-22

  • From This Site

    /content/journals/cas/10.2174/0118746098319674240827104612
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Health Japan 21 Analysis and Assessment Project. 2024 Available From: https://www.nibiohn.go.jp/eiken/kenkounippon21/en/
  2. United Nations Department of Economic and Social Affairs, Population Division. 2022 Available From: https://population.un.org/wpp/publications/ 2022
  3. Ministry of Health, Labour and Welfare, Japan. From Comprehensive Survey of Living Conditions. 2019 Available From: https://www.mhlw.go.jp/toukei/list/dl/20-21-h29.pdf
  4. Yudoh K Karasawa R Ishikawa J. Age-related Decrease of Sirtuin 2 Protein in Human Peripheral Blood Mononuclear Cells. Curr Aging Sci 2015 8 3 256 8
    [Google Scholar]
  5. Maiese K. Sirtuin biology in medicine, targeting new avenues of care in development, aging, and disease. Cambridge, Massachusetts Academic Press 2021
    [Google Scholar]
  6. Terauchi K. Kobayashi H. Yatabe K. Yui N. Fujiya H. Niki H. Musha H. Yudoh K. The NAD- Dependent deacetylase sirtuin-1 regulates the expression of osteogenic transcriptional activator runt-related transcription factor 2 (Runx2) and production of matrix metalloproteinase (MMP)- 13 in chondrocytes in osteoarthritis. Int. J. Mol. Sci. 2016 17 7 1019 10.3390/ijms17071019 27367673
    [Google Scholar]
  7. Kobayashi H. Terauchi K. Yui N. Yatabe K. Kamada T. Fujiya H. Niki H. Musha H. Yudoh K. The Nicotinamide Adenine Dinucleotide (NAD)-Dependent Deacetylase Sirtuin-1 Regulates Chondrocyte Energy Metabolism through the Modulation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) in Osteoarthritis(OA). J. Arthritis 2017 6 2 238 10.4172/2167‑7921.1000238
    [Google Scholar]
  8. Houtkooper R.H. Pirinen E. Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 2012 13 4 225 238 10.1038/nrm3293 22395773
    [Google Scholar]
  9. Carafa V Rotili D Forgione M Cuomo F Serretiello E Hailu GS Jarho E Lahtela-Kakkonen M Mai A Altucci L Sirtuin functions and modulation: From chemistry to the clinic. Clin Epigenetics 2016 8 61 10.1186/s13148‑016‑0224‑3
    [Google Scholar]
  10. Guarente L. Franklin H. Epstein Lecture: Sirtuins, aging, and medicine. N. Engl. J. Med. 2011 364 23 2235 2244 10.1056/NEJMra1100831 21651395
    [Google Scholar]
  11. Wątroba M Szukiewicz D The role of sirtuins in aging and age-related diseases. Adv Med Sci. 2016 61 1 52 62
    [Google Scholar]
  12. Dai H Sinclair DA Ellis JL Steegborn C Sirtuin activators and inhibitors: Promises, achievements, and challenges. Pharmacol Ther 2018 188 140 154 10.1016/j.pharmthera.2018.03.004
    [Google Scholar]
  13. Yang Y Liu Y Wang Y Chao Y Zhang J Jia Y Tie J Hu D. Regulation of SIRT1 and Its Roles in Inflammation. Front Immunol. 2022 13 31168 10.3389/fimmu.2022.831168
    [Google Scholar]
  14. Tao Z Jin Z Wu J Cai G Yu X. Sirtuin family in autoimmune diseases. Front Immunol. 2023 11 1186231 10.3389/fimmu.2023.1186231
    [Google Scholar]
  15. Sun K. Wu Y. Zeng Y. Xu J. Wu L. Li M. Shen B. The role of the sirtuin family in cartilage and osteoarthritis: Molecular mechanisms and therapeutic targets. Arthritis Res. Ther. 2022 24 1 286 10.1186/s13075‑022‑02983‑8 36585687
    [Google Scholar]
  16. Mouchiroud L. Houtkooper R.H. Moullan N. Katsyuba E. Ryu D. Cantó C. Mottis A. Jo Y.S. Viswanathan M. Schoonjans K. Guarente L. Auwerx J. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 2013 154 2 430 441 10.1016/j.cell.2013.06.016 23870130
    [Google Scholar]
  17. Imai S. Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 24 8 464 471 10.1016/j.tcb.2014.04.002 24786309
    [Google Scholar]
  18. D’Adamo S. Cetrullo S. Guidotti S. Borzì R.M. Flamigni F. Hydroxytyrosol modulates the levels of microRNA-9 and its target sirtuin-1 thereby counteracting oxidative stress-induced chondrocyte death. Osteoarthritis Cartilage 2016 2016 014 10.1016/j.joca.2016.11.014 27914878
    [Google Scholar]
  19. Pillai VB Gupta MP Is nuclear sirtuin SIRT6 a master regulator of immune function? Am J Physiol Endocrinol Metab. 2021 320 3 E399 E414 10.1152/ajpendo.00483.2020
    [Google Scholar]
  20. Oh H Kwak JS Yang S Gong MK Kim JH Rhee J Kim SK Kim HE Ryu JH Chun JS Reciprocal regulation by hypoxia-inducible factor-2α and the NAMPT-NAD(+)-SIRT axis in articular chondrocytes is involved in osteoarthritis. Osteoarthritis Cartilage 2015 23 12 2288 2296 10.1016/j.joca.2015.07.009
    [Google Scholar]
  21. Liu-Bryan R. Inflammation and intracellular metabolism: New targets in OA. Osteoarthritis Cartilage 2015 23 11 1835 1842 10.1016/j.joca.2014.12.016 26521729
    [Google Scholar]
  22. Hinton P.V. Rackard S.M. Kennedy O.D. In Vivo Osteocyte Mechanotransduction: Recent Developments and Future Directions. Curr. Osteoporos. Rep. 2018 16 6 746 753 10.1007/s11914‑018‑0485‑1 30406580
    [Google Scholar]
  23. Deng Z. Li Y. Liu H. Xiao S. Li L. Tian J. Cheng C. Zhang G. Zhang F. The role of sirtuin 1 and its activator, resveratrol in osteoarthritis. Biosci. Rep. 2019 39 5 BSR20190189 10.1042/BSR20190189 30996115
    [Google Scholar]
  24. Miller FJ Jr Hypertension and Mitochondrial Oxidative Stress Revisited: Sirtuin 3, the Improved "Antioxidant". Circ Res. 2020 126 4 453 455
    [Google Scholar]
  25. Wan X Garg NJ Sirtuin Control of Mitochondrial Dysfunction, Oxidative Stress, and Inflammation in Chagas Disease Models. Front Cell Infect Microbiol. 2021 11 693051 10.3389/fcimb.2021.693051
    [Google Scholar]
  26. Wu Q.J. Zhang T.N. Chen H.H. Yu X.F. Lv J.L. Liu Y.Y. Liu Y.S. Zheng G. Zhao J.Q. Wei Y.F. Guo J.Y. Liu F.H. Chang Q. Zhang Y.X. Liu C.G. Zhao Y.H. The sirtuin family in health and disease. Signal Transduct. Target. Ther. 2022 7 1 402 10.1038/s41392‑022‑01257‑8 36581622
    [Google Scholar]
  27. Kartha N Gianopulos JE Schrank Z Cavender SM Dobersch S Kynnap BD Wallace-Povirk A Wladyka CL Santana JF Kim JC Yu A Bridgwater CM Fuchs K Dysinger S Lampano AE Notta F Price DH Hsieh AC Hingorani SR Kugel S Sirtuin 6 is required for the integrated stress response and resistance to inhibition of transcriptional cyclin-dependent kinases. Sci Transl Med. 2023 15 694 eabn9674 10.1126/scitranslmed.abn9674
    [Google Scholar]
  28. Yang W. Kang X. Liu J. Li H. Ma Z. Jin X. Qian Z. Xie T. Qin N. Feng D. Pan W. Chen Q. Sun H. Wu S. Clock gene BMAl1 modulates human cartilage gene expression by crosstalk with sirt1. Endocrinology 2016 157 8 3096 3107 10.1210/en.2015‑2042 27253997
    [Google Scholar]
  29. Liu Y Zhang Z Liu C Zhang H. Sirtuins in osteoarthritis: Current understanding.. Front Immunol 2023 14 1140653 10.3389/fimmu.2023.1140653
    [Google Scholar]
  30. Yuan Y Zhang L Tong X Zhang M Zhao Y Guo J Lei L Chen X Tickner J Xu J Zou J. Mechanical Stress Regulates Bone Metabolism Through MicroRNAs. J Cell Physiol. 2017 232 6 1239 1245 10.1002/jcp.25688
    [Google Scholar]
  31. Maycas M Esbrit P Gortázar AR Molecular Mechanisms in Bone Mechanotransduction. J Musculoskelet Neuronal Interact. 2016 16 3 221 236 10.14670/HH‑11‑858
    [Google Scholar]
  32. Uda Y. Azab E. Sun N. Shi C. Pajevic P.D. Osteocyte Mechanobiology. Curr. Osteoporos. Rep. 2017 15 4 318 325 10.1007/s11914‑017‑0373‑0 28612339
    [Google Scholar]
  33. Chen X Yan J He F Zhong D Yang H Pei M Luo ZP Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway. Free Radic Biol Med. 2018 126 187 201 10.1016/j.freeradbiomed.2018.08.001
    [Google Scholar]
  34. Jiang S Zhang C Lu Y Yuan F Mechanical stress-caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1. J Biochem Mol Toxicol 2022 36 12 e23212 10.1002/jbt.23212
    [Google Scholar]
  35. Pardo PS Boriek AM SIRT1 Regulation in Ageing and Obesity.. Mech Ageing Dev. 2020 188 111249 10.1016/j.mad.2020.111249
    [Google Scholar]
  36. Shen P Deng X Chen Z Ba X Qin K Huang Y Huang Y Li T Yan J Tu S. SIRT1: A Potential Therapeutic Target in Autoimmune Diseases. Front Immunol. 2021 12 779177 10.3389/fimmu.2021.779177
    [Google Scholar]
  37. Wątroba M Szewczyk G Szukiewicz D. The Role of Sirtuin-1 (SIRT1) in the Physiology and Pathophysiology of the Human Placenta. Int J Mol Sci 2023 24 22 16210 10.3390/ijms242216210
    [Google Scholar]
  38. Chen Z Peng IC Cui X Li YS Chien S Shyy JY Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci U S A 2010 107 22 10268 73 10.1073/pnas.1003833107
    [Google Scholar]
  39. Suades R. Cosentino F. Sirtuin 1/soluble guanylyl cyclase: A nitric oxide-independent pathway to rescue ageing-induced vascular dysfunction. Cardiovasc. Res. 2019 115 3 485 487 10.1093/cvr/cvy297 30496343
    [Google Scholar]
  40. Liu J Bi X Chen T Zhang Q Wang SX Chiu JJ Liu GS Zhang Y Bu P Jiang F Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression. Cell Death Dis. 2015 6 7 e1827 10.1038/cddis.2015.193
    [Google Scholar]
  41. Lee S-I. Park K-H. Kim S-J. Kang Y-G. Lee Y-M. Kim E-C. Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells. Clin. Exp. Immunol. 2012 168 1 113 124 10.1111/j.1365‑2249.2011.04549.x 22385246
    [Google Scholar]
  42. Somemura S Kumai T Yatabe K Sasaki C Fujiya H Niki H Yudoh K. Physiologic Mechanical Stress Directly Induces Bone Formation by Activating Glucose Transporter 1 (Glut 1) in Osteoblasts, Inducing Signaling via NAD+-Dependent Deacetylase (Sirtuin 1) and Runt-Related Transcription Factor 2 (Runx2). Int. J. Mol. Sci. 2021 22 16 9070 10.3390/ijms22169070
    [Google Scholar]
  43. Li X. SIRT1 and energy metabolism. Acta Biochim. Biophys. Sin. (Shanghai) 2013 45 1 51 60 10.1093/abbs/gms108 23257294
    [Google Scholar]
  44. Chang H.C. Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol. Metab. 2014 25 3 138 145 10.1016/j.tem.2013.12.001 24388149
    [Google Scholar]
  45. Salminen A. Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev. 2012 11 2 230 241 10.1016/j.arr.2011.12.005 22186033
    [Google Scholar]
  46. Finkel T. The metabolic regulation of aging. Nat. Med. 2015 21 12 1416 1423 10.1038/nm.3998 26646498
    [Google Scholar]
  47. Matsuzaki T. Matsushita T. Takayama K. Matsumoto T. Nishida K. Kuroda R. Kurosaka M. Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann. Rheum. Dis. 2014 73 7 1397 1404 10.1136/annrheumdis‑2012‑202620 23723318
    [Google Scholar]
  48. Zheng Z Wang M Cheng C Liu D Wu L Zhu J Qian X. Ginsenoside Rb1 reduces H2O2‑induced HUVEC dysfunction by stimulating the sirtuin‑1/AMP‑activated protein kinase pathway. Mol. Med. Report 2020 22 1 247 256 10.3892/mmr.2020.11096
    [Google Scholar]
  49. Estienne A Bongrani A Ramé C Kurowska P Błaszczyk K Rak A Ducluzeau PH Froment P Dupont J Energy sensors and reproductive hypothalamo-pituitary ovarian axis (HPO) in female mammals: Role of mTOR (mammalian target of rapamycin), AMPK (AMP-activated protein kinase) and SIRT1 (Sirtuin 1). Mol Cell Endocrinol 2021 521 111113 10.1016/j.mce.2020.111113
    [Google Scholar]
  50. Xu Y Yu T Ma G Zheng L Jiang X Yang F Wang Z Li N He Z Song X Wen D Kong J Yu Y Cao L. Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway. Int J Biol Sci. 2021 17 12 3173 3187 10.7150/ijbs.62556
    [Google Scholar]
  51. North B.J. Rosenberg M.A. Jeganathan K.B. Hafner A.V. Michan S. Dai J. Baker D.J. Cen Y. Wu L.E. Sauve A.A. van Deursen J.M. Rosenzweig A. Sinclair D.A. SIRT 2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J. 2014 33 13 1438 1453 10.15252/embj.201386907 24825348
    [Google Scholar]
  52. Kumar R. Mohan N. Upadhyay A.D. Singh A.P. Sahu V. Dwivedi S. Dey A.B. Dey S. Identification of serum sirtuins as novel noninvasive protein markers for frailty. Aging Cell 2014 13 6 975 980 10.1111/acel.12260 25100619
    [Google Scholar]
  53. Wu B. You S. Qian H. Wu S. Lu S. Zhang Y. Sun Y. Zhang N. The role of SIRT2 in vascular‐related and heart‐related diseases: A review. J. Cell. Mol. Med. 2021 25 14 6470 6478 10.1111/jcmm.16618 34028177
    [Google Scholar]
  54. Zhang Y. Wang X. Li X.K. Lv S.J. Wang H.P. Liu Y. Zhou J. Gong H. Chen X.F. Ren S.C. Zhang H. Dai Y. Cai H. Yan B. Chen H.Z. Tang X. Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice. Eur. Heart J. 2023 44 29 2746 2759 10.1093/eurheartj/ehad381 37377116
    [Google Scholar]
  55. Liu W Wang Z Xia Y Kuang H Liu S Li L Tang C Yin D The balance of apoptosis and autophagy via regulation of the AMPK signal pathway in aging rat striatum during regular aerobic exercise. Exp Gerontol 2019 124 12 110647 10.1016/j.exger.2019.110647
    [Google Scholar]
  56. Salamon A Torok R Sumegi E Boros F Pesei ZG Fort Molnar M Veres G Zadori D Vecsei L Klivenyi P The effect of physical stimuli on the expression level of key elements in mitochondrial biogenesis. Neurosci Lett 2019 698 13 18 10.1016/j.neulet.2019.01.003
    [Google Scholar]
  57. Luo H. Mu W.C. Karki R. Chiang H.H. Mohrin M. Shin J.J. Ohkubo R. Ito K. Kanneganti T.D. Chen D. Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging. Cell Rep. 2019 26 4 945 954.e4 10.1016/j.celrep.2018.12.101 30673616
    [Google Scholar]
  58. Ryu D Jo YS Lo Sasso G Stein S Zhang H Perino A Lee JU Zeviani M Romand R Hottiger MO Schoonjans K Auwerx J.A A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function. Cell Metab 2014 20 5 856 869 10.1016/j.cmet.2014.08.001
    [Google Scholar]
  59. Lagunas-Rangel F.A. SIRT7 in the aging process. Cell. Mol. Life Sci. 2022 79 6 297 10.1007/s00018‑022‑04342‑x 35585284
    [Google Scholar]
  60. Raza U Tang X Liu Z Liu B. SIRT7: The seventh key to unlocking the mystery of aging. Physiol Rev 2024 104 1 253 280 10.1152/physrev.00044.2022
    [Google Scholar]
  61. Divya K.P. Kanwar N. Anuranjana P.V. Kumar G. Beegum F. George K.T. Kumar N. Nandakumar K. Kanwal A. SIRT6 in Regulation of Mitochondrial Damage and Associated Cardiac Dysfunctions: A Possible Therapeutic Target for CVDs. Cardiovasc. Toxicol. 2024 24 6 598 621 10.1007/s12012‑024‑09858‑1 38689163
    [Google Scholar]
  62. Behera B.P. Mishra S.R. Mahapatra K.K. Patil S. Efferth T. Bhutia S.K. SIRT1-activating butein inhibits arecoline-induced mitochondrial dysfunction through PGC1α and MTP18 in oral cancer. Phytomedicine 2024 129 155511 10.1016/j.phymed.2024.155511 38723523
    [Google Scholar]
/content/journals/cas/10.2174/0118746098319674240827104612
Loading
Nicotinamide Adenine Dinucleotide (NAD)-Dependent Protein Deacetylase, Sirtuin, as a Biomarker of Healthy Life Expectancy: A Mini-Review
Bentham Science Publishers ; https://doi.org/10.2174/0118746098319674240827104612
/content/journals/cas/10.2174/0118746098319674240827104612
/content/journals/cas/10.2174/0118746098319674240827104612
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: healthy life expectancy biomarkers ; Aging ; surrogate markers ; sirtuin

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test