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The Impact of Exercise Intervention on Biological and Functional Aging Through the Lens of Epigenetic Clocks

28 augustus 2026 bijgewerkt door: Ferenc Gergely Torma, Hungarian University of Sports Science

The Effects of Regular Exercise Training on Biological Aging in Older Adults: Investigation of Epigenetic and Functional Changes

This study investigated the effects of a structured 6-month high-intensity interval training (HIIT) program on blood DNA methylation-based measures of biological ageing, physical fitness, cardiovascular function, body composition, metabolic health, and the gut microbiome in adults aged 50-70 years.

Participants completed supervised exercise training three times per week for 6 months. Exercise intensity was individually prescribed based on estimated maximal heart rate (HRmax) and continuously monitored using Polar H10 heart-rate sensors. Perceived exertion was also assessed using the Borg Rating of Perceived Exertion scale to support safe and appropriate exercise intensity. The training program progressively increased the amount of high-intensity exercise over the intervention period. High-intensity intervals were performed above approximately 80% of estimated HRmax and were separated by 2-minute periods of active recovery.

Before and after the intervention, participants underwent physiological and functional assessments. Cardiovascular function was evaluated using echocardiography. Aerobic capacity was assessed using spiroergometry and the Chester Step Test for estimation of VO₂max. Muscular performance was evaluated using maximal vertical jump and handgrip strength tests. Exercise volume was quantified using oxygen-consumption and heart-rate data collected during exercise and expressed as MET-hours (MET-hrs), allowing the individual exercise dose accumulated during the intervention to be characterized.

Body composition was assessed using dual-energy X-ray absorptiometry (DEXA). Measurements included total and regional fat mass and fat-free mass, allowing changes in overall and regional body composition to be evaluated.

Blood samples were collected before and after the intervention, with participants refraining from exercise for 48 hours before blood collection. Samples were analyzed for selected metabolic and clinical biomarkers, including glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, and liver enzymes.

Blood samples were also used to assess blood DNA methylation-based measures of biological ageing. Genome-wide DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip. Several DNA methylation-based ageing measures were calculated, including DNAmFitAge, DNAmPhenoAge, DNAmGrimAge, Hannum Age, DunedinPACE, and the Horvath Skin & Blood and pan-tissue clocks. Changes in biological age acceleration were evaluated between baseline and post-intervention.

The gut microbiome was characterized using shotgun metagenomic sequencing to assess changes in microbial composition and functional potential following the exercise intervention.

The primary overall objective of the study was to determine whether the individual volume of exercise performed, quantified as MET-hours, was associated with changes in blood DNA methylation-based biological age acceleration following the 6-month intervention. The study also examined whether exercise volume and training-related changes were associated with changes in physical fitness, cardiovascular function, body composition, metabolic biomarkers, and gut microbiome characteristics. The results may contribute to understanding whether the amount of regular high-intensity exercise is related to biological ageing and other physiological adaptations in 50< years old adults.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

74

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • Pest County
      • Budapest, Pest County, Hongarije, 1123
        • Research Center for Molecular Exercise Science, Hungarian University of Sports Science, Alkotás st. 42-48

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Ja

Beschrijving

Inclusion Criteria:

  • Adults aged 50-70 years
  • Legal capacity to provide informed consent
  • Successful completion of a questionnaire-based and instrumental medical screening, confirming eligibility for physical exercise
  • Physical activity level between 1 and 5 METs/day, estimated based on a questionnaire

Exclusion Criteria:

  • Cardiovascular diseases that contraindicate physical exercise, including the presence of a pacemaker
  • Musculoskeletal conditions that contraindicate physical exercise
  • Acute or chronic kidney disease
  • Acute or chronic liver disease
  • Acute or chronic gastrointestinal disease
  • Acute or chronic infectious diseases or febrile conditions
  • Metabolic disorders or endocrine diseases
  • Bleeding disorders or coagulation abnormalities
  • Malignant diseases
  • Autoimmune diseases
  • Asthma
  • Psychiatric or mental disorders
  • Limited legal capacity or impaired ability to communicate
  • Chronic alcohol consumption

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Relative High Intensity Intervention Exercise Group for 6 month
Individuals over 50 years of age will undergo regular exercise training three times per week for 40-45 minutes using a high-intensity interval training (HIIT) modality for a period of 6 months. Following health screening and a 2-3-week habituation period, exercise intensity will be monitored and prescribed using a chest-strap heart rate monitoring system. Before and after the intervention, blood samples will be collected, and physiological and functional assessments will be conducted.
Participants completed supervised high-intensity interval training (HIIT) 3 times weekly for 6 months. Exercise intensity was prescribed relative to estimated maximal heart rate (HRmax; Tanaka formula) and was monitored continuously using Polar H10 heart-rate sensors. Sessions included a progressive warm-up, repeated 2-minute high-intensity intervals performed above 80% of HRmax, and 2-minute active recovery periods. Perceived exertion was also monitored using the Borg 0-10 RPE scale, with an upper target of 8. The protocol progressively increased training load: sessions 1-25 included five high-intensity intervals, sessions 26-45 six intervals, and sessions 46 onward seven intervals. Session duration increased from 34 to 38 minutes in the final phase.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Epigenetic Age Accelration
Tijdsspanne: Whole blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Whole blood samples were collected and analyzed using the Illumina EPIC BeadChip assay to quantify DNA methylation at specific CpG sites. DNA methylation-based biological age estimators, including DNAmFitAge, DNAmPhenoAge, and DNAmGrimAge, were calculated from the methylation data. Age acceleration values were expressed in years, and changes in these measures were correlated with changes in other primary and secondary outcome measures.
Whole blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Relative aerobic capaity spiroergometry: VO2 max measurement
Tijdsspanne: Spiriergomerty was conducted within 2 weeks before the first exercise session as the baseline measurement and after at least 48 hours, but no more than 14 days, after the final exercise session.
Relative aerobic capacity was evaluated using cardiopulmonary exercise testing (spiroergometry) and expressed as ml/kg/min
Spiriergomerty was conducted within 2 weeks before the first exercise session as the baseline measurement and after at least 48 hours, but no more than 14 days, after the final exercise session.
Relative aerobic capacity esimation: Chester step test
Tijdsspanne: The Chester Step Test was performed at the first exercise session, which served as the baseline assessment, and was repeated monthly thereafter to monitor changes in aerobic capacity throughout the intervention period.
The Chester Step Test was conducted to estimate changes in VO₂max during the 6-month intervention period. Heart rate responses recorded during each assessment were used to estimate relative aerobic capacity, expressed as mL/kg/min.
The Chester Step Test was performed at the first exercise session, which served as the baseline assessment, and was repeated monthly thereafter to monitor changes in aerobic capacity throughout the intervention period.
Exercise Volume: MET-hours
Tijdsspanne: Heart rate values and exercise duration were recorded during each exercise session throughout the 6-month intervention period.
Exercise volume was calculated based on estimated VO₂max, average and resting heart rate during exercise, and exercise duration. Exercise volume was expressed as MET-hours.
Heart rate values and exercise duration were recorded during each exercise session throughout the 6-month intervention period.
Total body muscular power
Tijdsspanne: Grip strength was measured within 2 weeks before the first exercise session as the baseline measurement. The second measurement was collected at least 48 hours, but no more than 14 days, after the final exercise session.
Total body muscular strength was measured using a handheld dynamometer, and grip force was expressed in kilograms (kg).
Grip strength was measured within 2 weeks before the first exercise session as the baseline measurement. The second measurement was collected at least 48 hours, but no more than 14 days, after the final exercise session.
Echocardiographic measurements
Tijdsspanne: Echocardiographic data was collected within 2 weeks before the first exercise session as the baseline measurement. The second second measurement was conducted at least 48 hours, but no more than 5 days, after the final exercise session.
Echocardiographic measurements included assessments of cardiac morphology and structure, as well as parameters of cardiac function. These measurements were used to characterize structural and functional cardiac adaptations and to evaluate changes in cardiovascular function over the course of the intervention.
Echocardiographic data was collected within 2 weeks before the first exercise session as the baseline measurement. The second second measurement was conducted at least 48 hours, but no more than 5 days, after the final exercise session.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Blood chemistry: LDL
Tijdsspanne: Blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Low-density lipoprotein cholesterol (LDL-C) was measured from venous blood reum samples as a marker of lipid metabolism and cardiovascular risk. LDL-C concentration was expressed in mmol/L.
Blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Blood chemistry: HDL
Tijdsspanne: Blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
High-density lipoprotein cholesterol (HDL) was measured from venous blood samples as a marker of lipid metabolism and cardiovascular health. HDL-C concentration was expressed in mmol/L.
Blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Blood chemistry: Fastung glucose
Tijdsspanne: Blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Fasting blood glucose was measured from venous blood samples following an overnight fast as a marker of glucose metabolism. Glucose concentration was expressed in mmol/L.
Blood was collected within 2 weeks before the first exercise session as the baseline measurement. The second blood sample was collected at least 48 hours, but no more than 5 days, after the final exercise session.
Fecal microbial status
Tijdsspanne: Fecal samples were collected within 2 weeks before the first exercise session as the baseline measurement. The second fecal sample was collected at least 48 hours, but no more than 2 weeks, after the final exercise session.
Gut microbiome composition and functional characteristics were assessed from fecal samples using shotgun metagenomic sequencing before and after the intervention. Microbiome composition was characterized at the species level, with individual taxa expressed as relative abundance.
Fecal samples were collected within 2 weeks before the first exercise session as the baseline measurement. The second fecal sample was collected at least 48 hours, but no more than 2 weeks, after the final exercise session.

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Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 mei 2022

Primaire voltooiing (Werkelijk)

1 mei 2024

Studie voltooiing (Werkelijk)

30 juni 2024

Studieregistratiedata

Eerst ingediend

26 augustus 2026

Eerst ingediend dat voldeed aan de QC-criteria

28 augustus 2026

Eerst geplaatst (Werkelijk)

2 september 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

2 september 2026

Laatste update ingediend die voldeed aan QC-criteria

28 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • NNGYK/14120-7/2025_FEP
  • 152986 (Ander subsidie-/financieringsnummer: NKFIH under the National Research Excellence Programme - STARTING_25)

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