Skip to content
2000
Volume 18, Issue 2
  • ISSN: 1874-6098
  • E-ISSN: 1874-6128
file format text download EPUB
file format pdf download PDF
side by side viewer icon HTML

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.

© 2025 Bentham Science Publishers
© 2025 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cas/10.2174/0118746098319674240827104612
2024-10-04
2025-08-19

  • From This Site

    /content/journals/cas/10.2174/0118746098319674240827104612
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
The full text of this item is not currently available.

References

  1. Health Japan 21 Analysis and Assessment Project.2024Available From: https://www.nibiohn.go.jp/eiken/kenkounippon21/en/
  2. United NationsDepartment of Economic and Social Affairs, Population Division.2022Available From: https://population.un.org/wpp/publications/ 2022
  3. Ministry of Health, Labour and Welfare, Japan.From Comprehensive Survey of Living Conditions.2019Available From: https://www.mhlw.go.jp/toukei/list/dl/20-21-h29.pdf
  4. YudohK KarasawaR IshikawaJ. Age-related Decrease of Sirtuin 2 Protein in Human Peripheral Blood Mononuclear Cells.Curr Aging Sci2015832568
     [Google Scholar]
  5. MaieseK. Sirtuin biology in medicine, targeting new avenues of care in development, aging, and disease.Cambridge, MassachusettsAcademic Press2021
     [Google Scholar]
  6. TerauchiK. KobayashiH. YatabeK. YuiN. FujiyaH. NikiH. MushaH. YudohK. 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.2016177101910.3390/ijms1707101927367673
     [Google Scholar]
  7. KobayashiH. TerauchiK. YuiN. YatabeK. KamadaT. FujiyaH. NikiH. MushaH. YudohK. 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. Arthritis20176223810.4172/2167‑7921.1000238
     [Google Scholar]
  8. HoutkooperR.H. PirinenE. AuwerxJ. Sirtuins as regulators of metabolism and healthspan.Nat. Rev. Mol. Cell Biol.201213422523810.1038/nrm329322395773
     [Google Scholar]
  9. CarafaV RotiliD ForgioneM CuomoF SerretielloE HailuGS JarhoE Lahtela-KakkonenM MaiA AltucciL Sirtuin functions and modulation: From chemistry to the clinic.Clin Epigenetics201686110.1186/s13148‑016‑0224‑3
     [Google Scholar]
  10. GuarenteL. Franklin H. Epstein Lecture: Sirtuins, aging, and medicine.N. Engl. J. Med.2011364232235224410.1056/NEJMra110083121651395
     [Google Scholar]
  11. WątrobaM SzukiewiczD The role of sirtuins in aging and age-related diseases.Adv Med Sci.20166115262
     [Google Scholar]
  12. DaiH SinclairDA EllisJL SteegbornC Sirtuin activators and inhibitors: Promises, achievements, and challenges.Pharmacol Ther201818814015410.1016/j.pharmthera.2018.03.004
     [Google Scholar]
  13. YangY LiuY WangY ChaoY ZhangJ JiaY TieJ HuD. Regulation of SIRT1 and Its Roles in Inflammation.Front Immunol.2022133116810.3389/fimmu.2022.831168
     [Google Scholar]
  14. TaoZ JinZ WuJ CaiG YuX. Sirtuin family in autoimmune diseases.Front Immunol.202311118623110.3389/fimmu.2023.1186231
     [Google Scholar]
  15. SunK. WuY. ZengY. XuJ. WuL. LiM. ShenB. The role of the sirtuin family in cartilage and osteoarthritis: Molecular mechanisms and therapeutic targets.Arthritis Res. Ther.202224128610.1186/s13075‑022‑02983‑836585687
     [Google Scholar]
  16. MouchiroudL. HoutkooperR.H. MoullanN. KatsyubaE. RyuD. CantóC. MottisA. JoY.S. ViswanathanM. SchoonjansK. GuarenteL. AuwerxJ. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling.Cell2013154243044110.1016/j.cell.2013.06.01623870130
     [Google Scholar]
  17. ImaiS. GuarenteL. NAD+ and sirtuins in aging and disease.Trends Cell Biol.201424846447110.1016/j.tcb.2014.04.00224786309
     [Google Scholar]
  18. D’AdamoS. CetrulloS. GuidottiS. BorzìR.M. FlamigniF. Hydroxytyrosol modulates the levels of microRNA-9 and its target sirtuin-1 thereby counteracting oxidative stress-induced chondrocyte death.Osteoarthritis Cartilage2016201601410.1016/j.joca.2016.11.01427914878
     [Google Scholar]
  19. PillaiVB GuptaMP Is nuclear sirtuin SIRT6 a master regulator of immune function?Am J Physiol Endocrinol Metab.20213203E399E41410.1152/ajpendo.00483.2020
     [Google Scholar]
  20. OhH KwakJS YangS GongMK KimJH RheeJ KimSK KimHE RyuJH ChunJS Reciprocal regulation by hypoxia-inducible factor-2α and the NAMPT-NAD(+)-SIRT axis in articular chondrocytes is involved in osteoarthritis.Osteoarthritis Cartilage201523122288229610.1016/j.joca.2015.07.009
     [Google Scholar]
  21. Liu-BryanR. Inflammation and intracellular metabolism: New targets in OA.Osteoarthritis Cartilage201523111835184210.1016/j.joca.2014.12.01626521729
     [Google Scholar]
  22. HintonP.V. RackardS.M. KennedyO.D. In Vivo Osteocyte Mechanotransduction: Recent Developments and Future Directions.Curr. Osteoporos. Rep.201816674675310.1007/s11914‑018‑0485‑130406580
     [Google Scholar]
  23. DengZ. LiY. LiuH. XiaoS. LiL. TianJ. ChengC. ZhangG. ZhangF. The role of sirtuin 1 and its activator, resveratrol in osteoarthritis.Biosci. Rep.2019395BSR2019018910.1042/BSR2019018930996115
     [Google Scholar]
  24. MillerFJJr Hypertension and Mitochondrial Oxidative Stress Revisited: Sirtuin 3, the Improved "Antioxidant".Circ Res.20201264453455
     [Google Scholar]
  25. WanX GargNJ Sirtuin Control of Mitochondrial Dysfunction, Oxidative Stress, and Inflammation in Chagas Disease Models.Front Cell Infect Microbiol.20211169305110.3389/fcimb.2021.693051
     [Google Scholar]
  26. WuQ.J. ZhangT.N. ChenH.H. YuX.F. LvJ.L. LiuY.Y. LiuY.S. ZhengG. ZhaoJ.Q. WeiY.F. GuoJ.Y. LiuF.H. ChangQ. ZhangY.X. LiuC.G. ZhaoY.H. The sirtuin family in health and disease.Signal Transduct. Target. Ther.20227140210.1038/s41392‑022‑01257‑836581622
     [Google Scholar]
  27. KarthaN GianopulosJE SchrankZ CavenderSM DoberschS KynnapBD Wallace-PovirkA WladykaCL SantanaJF KimJC YuA BridgwaterCM FuchsK DysingerS LampanoAE NottaF PriceDH HsiehAC HingoraniSR KugelS Sirtuin 6 is required for the integrated stress response and resistance to inhibition of transcriptional cyclin-dependent kinases.Sci Transl Med.202315694eabn967410.1126/scitranslmed.abn9674
     [Google Scholar]
  28. YangW. KangX. LiuJ. LiH. MaZ. JinX. QianZ. XieT. QinN. FengD. PanW. ChenQ. SunH. WuS. Clock gene BMAl1 modulates human cartilage gene expression by crosstalk with sirt1.Endocrinology201615783096310710.1210/en.2015‑204227253997
     [Google Scholar]
  29. LiuY ZhangZ LiuC ZhangH. Sirtuins in osteoarthritis: Current understanding..Front Immunol202314114065310.3389/fimmu.2023.1140653
     [Google Scholar]
  30. YuanY ZhangL TongX ZhangM ZhaoY GuoJ LeiL ChenX TicknerJ XuJ ZouJ. Mechanical Stress Regulates Bone Metabolism Through MicroRNAs.J Cell Physiol.201723261239124510.1002/jcp.25688
     [Google Scholar]
  31. MaycasM EsbritP GortázarAR Molecular Mechanisms in Bone Mechanotransduction.J Musculoskelet Neuronal Interact.201616322123610.14670/HH‑11‑858
     [Google Scholar]
  32. UdaY. AzabE. SunN. ShiC. PajevicP.D. Osteocyte Mechanobiology.Curr. Osteoporos. Rep.201715431832510.1007/s11914‑017‑0373‑028612339
     [Google Scholar]
  33. ChenX YanJ HeF ZhongD YangH PeiM LuoZP 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.201812618720110.1016/j.freeradbiomed.2018.08.001
     [Google Scholar]
  34. JiangS ZhangC LuY YuanF Mechanical stress-caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1.J Biochem Mol Toxicol20223612e2321210.1002/jbt.23212
     [Google Scholar]
  35. PardoPS BoriekAM SIRT1 Regulation in Ageing and Obesity..Mech Ageing Dev.202018811124910.1016/j.mad.2020.111249
     [Google Scholar]
  36. ShenP DengX ChenZ BaX QinK HuangY HuangY LiT YanJ TuS. SIRT1: A Potential Therapeutic Target in Autoimmune Diseases.Front Immunol.20211277917710.3389/fimmu.2021.779177
     [Google Scholar]
  37. WątrobaM SzewczykG SzukiewiczD. The Role of Sirtuin-1 (SIRT1) in the Physiology and Pathophysiology of the Human Placenta.Int J Mol Sci202324221621010.3390/ijms242216210
     [Google Scholar]
  38. ChenZ PengIC CuiX LiYS ChienS ShyyJY Shear stress, SIRT1, and vascular homeostasis.Proc Natl Acad Sci USA201010722102687310.1073/pnas.1003833107
     [Google Scholar]
  39. SuadesR. CosentinoF. Sirtuin 1/soluble guanylyl cyclase: A nitric oxide-independent pathway to rescue ageing-induced vascular dysfunction.Cardiovasc. Res.2019115348548710.1093/cvr/cvy29730496343
     [Google Scholar]
  40. LiuJ BiX ChenT ZhangQ WangSX ChiuJJ LiuGS ZhangY BuP JiangF Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression.Cell Death Dis.201567e182710.1038/cddis.2015.193
     [Google Scholar]
  41. LeeS-I. ParkK-H. KimS-J. KangY-G. LeeY-M. KimE-C. Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells.Clin. Exp. Immunol.2012168111312410.1111/j.1365‑2249.2011.04549.x22385246
     [Google Scholar]
  42. SomemuraS KumaiT YatabeK SasakiC FujiyaH NikiH YudohK. 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.20212216907010.3390/ijms22169070
     [Google Scholar]
  43. LiX. SIRT1 and energy metabolism.Acta Biochim. Biophys. Sin. (Shanghai)2013451516010.1093/abbs/gms10823257294
     [Google Scholar]
  44. ChangH.C. GuarenteL. SIRT1 and other sirtuins in metabolism.Trends Endocrinol. Metab.201425313814510.1016/j.tem.2013.12.00124388149
     [Google Scholar]
  45. SalminenA. KaarnirantaK. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network.Ageing Res. Rev.201211223024110.1016/j.arr.2011.12.00522186033
     [Google Scholar]
  46. FinkelT. The metabolic regulation of aging.Nat. Med.201521121416142310.1038/nm.399826646498
     [Google Scholar]
  47. MatsuzakiT. MatsushitaT. TakayamaK. MatsumotoT. NishidaK. KurodaR. KurosakaM. Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice.Ann. Rheum. Dis.20147371397140410.1136/annrheumdis‑2012‑20262023723318
     [Google Scholar]
  48. ZhengZ WangM ChengC LiuD WuL ZhuJ QianX. Ginsenoside Rb1 reduces H2O2‑induced HUVEC dysfunction by stimulating the sirtuin‑1/AMP‑activated protein kinase pathway.Mol. Med. Report202022124725610.3892/mmr.2020.11096
     [Google Scholar]
  49. EstienneA BongraniA RaméC KurowskaP BłaszczykK RakA DucluzeauPH FromentP DupontJ 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 Endocrinol202152111111310.1016/j.mce.2020.111113
     [Google Scholar]
  50. XuY YuT MaG ZhengL JiangX YangF WangZ LiN HeZ SongX WenD KongJ YuY CaoL. Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway.Int J Biol Sci.202117123173318710.7150/ijbs.62556
     [Google Scholar]
  51. NorthB.J. RosenbergM.A. JeganathanK.B. HafnerA.V. MichanS. DaiJ. BakerD.J. CenY. WuL.E. SauveA.A. van DeursenJ.M. RosenzweigA. SinclairD.A. SIRT 2 induces the checkpoint kinase BubR1 to increase lifespan.EMBO J.201433131438145310.15252/embj.20138690724825348
     [Google Scholar]
  52. KumarR. MohanN. UpadhyayA.D. SinghA.P. SahuV. DwivediS. DeyA.B. DeyS. Identification of serum sirtuins as novel noninvasive protein markers for frailty.Aging Cell201413697598010.1111/acel.1226025100619
     [Google Scholar]
  53. WuB. YouS. QianH. WuS. LuS. ZhangY. SunY. ZhangN. The role of SIRT2 in vascular‐related and heart-related diseases: A review.J. Cell. Mol. Med.202125146470647810.1111/jcmm.1661834028177
     [Google Scholar]
  54. ZhangY. WangX. LiX.K. LvS.J. WangH.P. LiuY. ZhouJ. GongH. ChenX.F. RenS.C. ZhangH. DaiY. CaiH. YanB. ChenH.Z. TangX. Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice.Eur. Heart J.202344292746275910.1093/eurheartj/ehad38137377116
     [Google Scholar]
  55. LiuW WangZ XiaY KuangH LiuS LiL TangC YinD The balance of apoptosis and autophagy via regulation of the AMPK signal pathway in aging rat striatum during regular aerobic exercise.Exp Gerontol20191241211064710.1016/j.exger.2019.110647
     [Google Scholar]
  56. SalamonA TorokR SumegiE BorosF PeseiZG Fort MolnarM VeresG ZadoriD VecseiL KlivenyiP The effect of physical stimuli on the expression level of key elements in mitochondrial biogenesis.Neurosci Lett2019698131810.1016/j.neulet.2019.01.003
     [Google Scholar]
  57. LuoH. MuW.C. KarkiR. ChiangH.H. MohrinM. ShinJ.J. OhkuboR. ItoK. KannegantiT.D. ChenD. Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging.Cell Rep.2019264945954.e410.1016/j.celrep.2018.12.10130673616
     [Google Scholar]
  58. RyuD JoYS Lo SassoG SteinS ZhangH PerinoA LeeJU ZevianiM RomandR HottigerMO SchoonjansK AuwerxJ.A A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function.Cell Metab201420585686910.1016/j.cmet.2014.08.001
     [Google Scholar]
  59. Lagunas-RangelF.A. SIRT7 in the aging process.Cell. Mol. Life Sci.202279629710.1007/s00018‑022‑04342‑x35585284
     [Google Scholar]
  60. RazaU TangX LiuZ LiuB. SIRT7: The seventh key to unlocking the mystery of aging.Physiol Rev2024104125328010.1152/physrev.00044.2022
     [Google Scholar]
  61. DivyaK.P. KanwarN. AnuranjanaP.V. KumarG. BeegumF. GeorgeK.T. KumarN. NandakumarK. KanwalA. SIRT6 in Regulation of Mitochondrial Damage and Associated Cardiac Dysfunctions: A Possible Therapeutic Target for CVDs.Cardiovasc. Toxicol.202424659862110.1007/s12012‑024‑09858‑138689163
     [Google Scholar]
  62. BeheraB.P. MishraS.R. MahapatraK.K. PatilS. EfferthT. BhutiaS.K. SIRT1-activating butein inhibits arecoline-induced mitochondrial dysfunction through PGC1α and MTP18 in oral cancer.Phytomedicine202412915551110.1016/j.phymed.2024.15551138723523
     [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
Curr Aging Sci 18, 95 (2025); 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
Keyword(s): Aging; healthy life expectancy biomarkers; mitochondria; nicotinamide adenine dinucleotide (NAD); sirtuin; surrogate markers

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