Skip to content
2000
Volume 3, Issue 1
  • ISSN: 2210-299X
  • E-ISSN: 2210-3007
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Introduction

The escalation of metabolic imbalance in obesity not only diminishes lifespan but also accelerates the cellular and biomolecular mechanisms of aging. This study aimed to explore the effect of intermittent fasting on FOXO3 expression, proteasome activity, and oxidative stress in obesity as parameters that play a role in the aging molecular process.

Methods

A randomized clinical trial was conducted in Jakarta. The study enrolled 50 obese males, divided into a control group of 25 individuals and an intervention group of 25 individuals. Over the course of 8 weeks, the intervention group adhered to a 5:2 intermittent fasting regimen, fasting for two days each week, specifically on Mondays and Thursdays. The food intake was monitored through food records and analyzed using the NutriSurvey 2007 program. Prior to and following the intervention, whole blood samples were collected for the analysis of FOXO3 expression, proteasome activity, and oxidative stress, assessed by measuring carbonyl, reduced glutathione/GSH, and total antioxidant capacity.

Results

The fasting group exhibited a lower consumption of complex carbohydrates, fats, and proteins compared to the control. Notably, there was a significant increase in FOXO3 expression and proteasome activity observed in the intermittent fasting group compared to the control. Furthermore, oxidative stress was mitigated in the intermittent fasting group, as evidenced by a decrease in carbonyl and an increase in GSH levels and total antioxidant capacity.

Conclusion

The 5:2 intermittent fasting over an 8-week period promotes increased FOXO3 expression and proteasome activity while reducing oxidative stress, thereby potentially delaying the aging process in obesity.

Clinical Trial Registration No.

This study has been registered online at www.clinicaltrial.gov (ID: NCT04319133).

© 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/cis/10.2174/012210299X400288250922114425
2025-10-02
2025-12-10

  • From This Site

    /content/journals/cis/10.2174/012210299X400288250922114425
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cis/3/1/CIS-3-E2210299X400288.html?itemId=/content/journals/cis/10.2174/012210299X400288250922114425&mimeType=html&fmt=ahah

References

  1. PurnellJ.Q. Definitions, classification, and epidemiology of obesity.EndotextSouth DartmouthMDText.com, Inc2018
     [Google Scholar]
  2. NybergS.T. BattyG.D. PenttiJ. VirtanenM. AlfredssonL. FranssonE.I. GoldbergM. HeikkiläK. JokelaM. KnutssonA. KoskenvuoM. LallukkaT. LeineweberC. LindbohmJ.V. MadsenI.E.H. Magnusson HansonL.L. NordinM. OksanenT. PietiläinenO. RahkonenO. RuguliesR. ShipleyM.J. StenholmS. SuominenS. TheorellT. VahteraJ. WesterholmP.J.M. WesterlundH. ZinsM. HamerM. Singh-ManouxA. BellJ.A. FerrieJ.E. KivimäkiM. Obesity and loss of disease-free years owing to major non-communicable diseases: A multicohort study.Lancet Public Health2018310e490e49710.1016/S2468‑2667(18)30139‑730177479
     [Google Scholar]
  3. SalvestriniV. SellC. LorenziniA. Obesity may accelerate the aging process.Front Endocrinol (Lausanne)20191026610.3389/fendo.2019.0026631130916
     [Google Scholar]
  4. KorovilaI. HugoM. CastroJ.P. WeberD. HöhnA. GruneT. JungT. Proteostasis, oxidative stress and aging.Redox Biol20171355056710.1016/j.redox.2017.07.00828763764
     [Google Scholar]
  5. HippM.S. KasturiP. HartlF.U. The proteostasis network and its decline in ageing.Nat Rev Mol Cell Biol201920742143510.1038/s41580‑019‑0101‑y30733602
     [Google Scholar]
  6. KlaipsC.L. JayarajG.G. HartlF.U. Pathways of cellular proteostasis in aging and disease.J Cell Biol20182171516310.1083/jcb.20170907229127110
     [Google Scholar]
  7. Díaz-RuizA. Guzmán-RuizR. MorenoN.R. García-RiosA. Delgado-CasadoN. MembrivesA. TúnezI. El BekayR. Fernández-RealJ.M. TovarS. DiéguezC. TinahonesF.J. Vázquez-MartínezR. López-MirandaJ. MalagónM.M. Proteasome dysfunction associated to oxidative stress and proteotoxicity in adipocytes compromises insulin sensitivity in human obesity.Antioxid Redox Signal201523759761210.1089/ars.2014.593925714483
     [Google Scholar]
  8. KorovilaI. HöhnA. JungT. GruneT. OttC. Reduced liver autophagy in high-fat diet induced liver steatosis in new zealand obese mice.Antioxidants202110450110.3390/antiox1004050133804819
     [Google Scholar]
  9. MorrisB.J. WillcoxD.C. DonlonT.A. WillcoxB.J. FOXO3: a major gene for human longevity: A mini-review.Gerontology201561651552510.1159/00037523525832544
     [Google Scholar]
  10. FasanoC. DisciglioV. BertoraS. Lepore SignorileM. SimoneC. FOXO3a from the nucleus to the mitochondria: A round trip in cellular stress response.Cells201989111010.3390/cells809111031546924
     [Google Scholar]
  11. AudesseA.J. DhakalS. HassellL.A. GardellZ. NemtsovaY. WebbA.E. FOXO3 directly regulates an autophagy network to functionally regulate proteostasis in adult neural stem cells.PLoS Genet2019154e100809710.1371/journal.pgen.100809730973875
     [Google Scholar]
  12. WaziryR. RyanC.P. CorcoranD.L. HuffmanK.M. KoborM.S. KothariM. GrafG.H. KrausV.B. KrausW.E. LinD.T.S. PieperC.F. RamakerM.E. BhapkarM. DasS.K. FerrucciL. HastingsW.J. KebbeM. ParkerD.C. RacetteS.B. ShalevI. SchillingB. BelskyD.W. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.Nat Aging20233324825710.1038/s43587‑022‑00357‑y37118425
     [Google Scholar]
  13. StockmanM.C. ThomasD. BurkeJ. ApovianC.M. Intermittent fasting: Is the wait worth the weight?Curr Obes Rep20187217218510.1007/s13679‑018‑0308‑929700718
     [Google Scholar]
  14. SongD.K. KimY.W. Beneficial effects of intermittent fasting: A narrative review.J Yeungnam Med Sci202340141110.12701/jyms.2022.0001035368155
     [Google Scholar]
  15. HardianyNS The mRNA expression of Forkhead box O3a (FOXO3a) as a longevity-associated gene in leucocytes of elderly women.J Pak Med Assoc2021712S74
     [Google Scholar]
  16. HardianyN.S. SadikinM. SiregarN. WanandiS.I. The suppression of manganese superoxide dismutase decreased the survival of human glioblastoma multiforme T98G cells.Med J Indones2017261192510.13181/mji.v26i1.1511
     [Google Scholar]
  17. LivakK.J. SchmittgenT.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.Methods200125440240810.1006/meth.2001.126211846609
     [Google Scholar]
  18. HardianyN.S. KarmanA.P. CalistaA.S.P. AnindyanariB.G. RahardjoD.E. NoviraP.R. TaufiqR.R. ImtiyazS. AntariantoR.D. The effect of fasting on oxidative stress in the vital organs of new zealand white rabbit.Rep Biochem Mol Biol202211219019936164627
     [Google Scholar]
  19. WeirC.B. JanA. BMI Classification Percentile and Cut Off Points.StatPearlsTreasure Island, FLStatPearls Publishing2025
     [Google Scholar]
  20. <comment xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">Hasil utama riskesdas penyakit tidak menular 2018.</comment>2018
  21. AbadiniD. WuryaningsihC.E. Determinants of physical activity of adult office workers in Jakarta in 2018.J Promosi Kesehatan Indonesia20181411510.14710/jpki.14.1.15‑28
     [Google Scholar]
  22. BrogiS. TabanelliR. PucaS. CalderoneV. Intermittent fasting: Myths, fakes and truth on this dietary regimen approach.Foods20241313196010.3390/foods1313196038998465
     [Google Scholar]
  23. ScholtensE.L. KrebsJ.D. CorleyB.T. HallR.M. Intermittent fasting 5:2 diet: What is the macronutrient and micronutrient intake and composition?Clin Nutr202039113354336010.1016/j.clnu.2020.02.02232199696
     [Google Scholar]
  24. ElorteguiP.P. RolandsM.R. EldridgeA.L. EldridgeA.L. KassisA. MainardiF. A meta-analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time-restricted eating for weight loss.Obesity (Silver Spring)2022•••11336349432
     [Google Scholar]
  25. BiobakuF. GhanimH. BatraM. DandonaP. Macronutrient-mediated inflammation and oxidative stress: Relevance to insulin resistance, obesity, and atherogenesis.J Clin Endocrinol Metab2019104126118612810.1210/jc.2018‑0183331219543
     [Google Scholar]
  26. HardianyN.S. Remifta PutraM.A. PenantianR.M. AntariantoR.D. Effects of fasting on FOXO3 expression as an anti-aging biomarker in the liver.Heliyon202392e1314410.1016/j.heliyon.2023.e1314436718153
     [Google Scholar]
  27. ChengM. NieY. SongM. ChenF. YuY. Forkhead box O proteins: Steering the course of stem cell fate.Cell Regen (Lond)2024131710.1186/s13619‑024‑00190‑138466341
     [Google Scholar]
  28. YuliyanasariN. ZamriE.N. RejekiP.S. MiftahussururM. The impact of ten days of periodic fasting on the modulation of the longevity gene in overweight and obese individuals: A quasi-experimental study.Nutrients20241618311210.3390/nu1618311239339719
     [Google Scholar]
  29. BarteltA. WidenmaierS.B. Proteostasis in thermogenesis and obesity.Biol Chem202040191019103010.1515/hsz‑2019‑042732061163
     [Google Scholar]
  30. Ignacio-SouzaL.M. BombassaroB. PascoalL.B. PortovedoM.A. RazolliD.S. CoopeA. VictorioS.C. de MouraR.F. NascimentoL.F. ArrudaA.P. AnheG.F. MilanskiM. VellosoL.A. Defective regulation of the ubiquitin/proteasome system in the hypothalamus of obese male mice.Endocrinology201415582831284410.1210/en.2014‑109024892821
     [Google Scholar]
  31. McMurrayF. PattenD.A. HarperM.E. Reactive oxygen species and oxidative stress in obesity-recent findings and empirical approaches.Obesity (Silver Spring)201624112301231010.1002/oby.2165427804267
     [Google Scholar]
  32. PerluigiM. Di DomenicoF. ButterfieldD.A. Oxidative damage in neurodegeneration: Roles in the pathogenesis and progression of Alzheimer disease.Physiol Rev2024104110319710.1152/physrev.00030.202237843394
     [Google Scholar]
  33. ElluluM.S. PatimahI. Khaza’aiH. RahmatA. AbedY. Obesity and inflammation: The linking mechanism and the complications.Arch Med Sci20174485186310.5114/aoms.2016.5892828721154
     [Google Scholar]
  34. MarsegliaL. MantiS. D’AngeloG. NicoteraA. ParisiE. Di RosaG. GittoE. ArrigoT. Oxidative stress in obesity: A critical component in human diseases.Int J Mol Sci201416137840010.3390/ijms1601037825548896
     [Google Scholar]
  35. EpingeacM.E. GamanM.A. DiaconuC.C. GamanA.M. Crosstalk between oxidative stress and inflammation in obesity.Revista de Chimie202071122823210.37358/RC.20.1.7837
     [Google Scholar]
  36. FurukawaS. FujitaT. ShimabukuroM. IwakiM. YamadaY. NakajimaY. NakayamaO. MakishimaM. MatsudaM. ShimomuraI. Increased oxidative stress in obesity and its impact on metabolic syndrome.J Clin Invest2004114121752176110.1172/JCI2162515599400
     [Google Scholar]
  37. JuanC.A. Pérez de la LastraJ.M. PlouF.J. Pérez-LebeñaE. The chemistry of reactive oxygen species (ROS) revisited: Outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies.Int J Mol Sci2021229464210.3390/ijms2209464233924958
     [Google Scholar]
  38. Raji-AmirhasaniA. KhaksariM. SoltaniZ. SaberiS. IranpourM. Darvishzadeh MahaniF. HajializadehZ. SabetN. Beneficial effects of time and energy restriction diets on the development of experimental acute kidney injury in Rat: Bax/Bcl-2 and histopathological evaluation.BMC Nephrol20232415910.1186/s12882‑023‑03104‑636941590
     [Google Scholar]
  39. MiftahussururM. YuliyanasariN. RejekiP.S. HidayatiH.B. SubsomwongP. The effect of intermittent fasting on preventing obesity-related early aging from a molecular and cellular perspective.J Med Life202417326127210.25122/jml‑2023‑037039044934
     [Google Scholar]
  40. AsadiH. AbolfathiA.A. BadalzadehR. MajidiniaM. YaghoubiA. AsadiM. YousefiB. Effects of ramadan fasting on serum amyloid A and protein carbonyl group levels in patients with cardiovascular diseases.J Cardiovasc Thorac Res201572555910.15171/jcvtr.2015.1226191392
     [Google Scholar]
  41. KuzniakO.V. SorochynskaO.M. BayliakM.M. KlonovskyiA.Y. VasylykY.V. SemchyshynH.M. StoreyK.B. GaraschukO. LushchakV.I. Feeding to satiation induces mild oxidative/carbonyl stress in the brain of young mice.EXCLI J202221779235145367
     [Google Scholar]
  42. ChausseB. Vieira-LaraM.A. SanchezA.B. MedeirosM.H.G. KowaltowskiA.J. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.PLoS One2015103e012041310.1371/journal.pone.012041325749501
     [Google Scholar]
/content/journals/cis/10.2174/012210299X400288250922114425
Loading
The Effect of Intermittent Fasting on FOXO3 Expression, Proteasome Activity and Oxidative Stress in Obese Men: A Clinical Trial
Curr. Indian Sci. 3, E2210299X400288 (2025); https://doi.org/10.2174/012210299X400288250922114425
/content/journals/cis/10.2174/012210299X400288250922114425
/content/journals/cis/10.2174/012210299X400288250922114425
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Aging; Degenerative disease; Intermittent fasting; Obesity; Oxidative stress; Proteasome

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