The effect of physical exercise on markers of aging

ISRCTN	ISRCTN16898870
DOI	https://doi.org/10.1186/ISRCTN16898870
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	HUS/467/2022
Sponsor	Folkhälsans Forskningscentrum
Funders	Samfundet Folkhälsan, Medicinska Understödsföreningen Liv och Hälsa, Finska Läkaresällskapet

Submission date: 19/04/2022
Registration date: 25/04/2022
Last edited: 03/10/2023

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
As we age the body functions deteriorate and the body is more susceptible to chronic diseases. That is why it is important to promote healthy aging in order to preserve independence and quality of life in old age. Healthy ageing can be advanced with regular physical activity and exercise. Physical activity is one of the most important ways to slow down the physical, mental and cognitive decline associated with aging. Aging is a complex process in which many different factors interact. There are different aging measures which try to describe the biological aging process. These measures can be used to assess if a treatment such as physical exercise is effective and advance healthy aging. Therefore, the aim of this study is to investigate the effect of the 6-month home-based exercise training on different biological aging measures and other markers of aging.

Who can participate?
50-70-year old physically inactive adults who don’t smoke and don’t have major chronic diseases.

What does the study involve?
Participants are allocated to one of two groups. Those in the exercise group train for 24 weeks according to a training program consisting of Nordic walking two or three times per week and resistance training with elastic bands two times per week. Participants are instructed three times before they start to exercise but otherwise they train independently at home and are contacted by phone and messages. Those in the control group continue their normal life. All participants take part in the same assessments and measurements before and after the 24-week study period. These include questionnaires and assessments done at rest, tests for functional capacity and physical performance, fasting blood samples and oral glucose tolerance tests. In addition, each participant will measure their physical activity and sleep at home for 7 days.

What are the possible benefits and risks of participating?
All participants receive information about their health, functional capacity and physical performance. Participants in the exercise group receive three teaching sessions for the exercise training and a training program. This training program is given to all participants after the study, especially recommended if proven beneficial. Possible risks related to physical exercise include muscle soreness and pain and injuries e.g. in the ligaments but risks are estimated to be low when starting easily enough at low or moderate intensity. Slight pain and bruises can emerge when drawing blood samples.

Where is the study run from?
Samfundet Folkhälsan (Finland)

When is the study starting and how long is it expected to run for?
June 2022 to December 2025

Who is funding the study?
1. Samfundet Folkhälsan (Finland)
2. Medicinska Understödsföreningen Liv och Hälsa (Finland)
3. Finska Läkaresällskapet (Finland)

Who is the main contact?
Niko Wasenius
niko.wasenius@helsinki.fi

Contact information

Dr Niko Wasenius
Principal investigator

Topeliuksenkatu 20
Helsinki
00250
Finland

ORCID ID	0000-0002-9007-6660
Phone	+358 (0)443714921
Email	niko.wasenius@helsinki.fi

Dr Niko Wasenius
Scientific

Topeliuksenkatu 20
Helsinki
00250
Finland

ORCID ID	0000-0002-9007-6660
Phone	+358 (0)443714921
Email	niko.wasenius@helsinki.fi

Dr Niko Wasenius
Public

Topeliuksenkatu 20
Helsinki
00250
Finland

ORCID ID	0000-0002-9007-6660
Phone	+358 (0)443714921
Email	niko.wasenius@helsinki.fi

Study information

Primary study design	Interventional
Study design	Single-centre interventional randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	The effect of physical eXercise on phenotypic AGE acceleration in adults approaching later life: a randomized controlled trial
Study acronym	XAGE
Study objectives	The 24-week physical exercise intervention has a beneficial effect on phenotypic age and phenotypic age acceleration and other phenotypic markers of aging in people approaching later life.
Ethics approval(s)	Approved 12/04/2022, Helsingin ja Uudenmaan sairaanhoitopiirin alueellinen lääketieteellinen tutkimuseettinen toimikunta (The Ethics Committee of the Helsinki and Uusimaa Hospital District; PL 705, 00029 HUS, Finland / Biomedicum Helsinki 2C, 7. krs, Tukholmankatu 8 C, 00290 Helsinki, Finland; +358 (0)40 359 4618, eettiset.toimikunnat@hus.fi), ref: HUS/467/2022
Health condition(s) or problem(s) studied	Effects of physical exercise on markers of aging in physically inactive adults approaching later life
Intervention	Participants are randomized 1:1 either to the control group or the exercise intervention group after all the baseline measurements. A computerized randomization sequence is used, stratified by sex and age with a 1:1 allocation using block sizes of 10–15. Control group: Participants will receive the national physical activity guidelines. Exercise intervention group: A 24-week Nordic walking and resistance training program where training load is planned to increase progressively. Nordic walking 2-3 times a week for 30-60 minutes at the relative intensity of 50-70 % of heart rate reserve and resistance training for the main muscle groups with elastic bands 2 times a week for 30 minutes. Training program and exercises are instructed to the participants before the intervention. Otherwise participants perform exercises at home without supervision but are contacted (calls/messages) according to the predetermined schedule.
Intervention type	Behavioural
Primary outcome measure(s)	1. Phenotypic age measured using a fasting blood sample as a linear combination of chronological age and nine multisystem clinical chemistry biomarkers at baseline and 24 weeks 2. Phenotypic age acceleration measured using a fasting blood sample as a residual of phenotypic age after accounting for chronological age at baseline and 24 weeks
Key secondary outcome measure(s)	1. (Relative) leucocyte telomere length is measured from whole blood leukocyte DNA using quantitative real-time polymerase chain reaction at baseline and 24 weeks 2. DNA methylation is measured from blood and saliva samples using techniques based on methylation arrays to compute b (% methylation) values for each CpG site at baseline and 24 weeks 3. Epigenetic clocks are measured from blood and buccal swab samples using the methylation information at baseline and 24 weeks (updated 04/05/2022, previously: Epigenetic clocks are measured from blood and saliva samples using the methylation information at baseline and 24 weeks) 4. Mitochondrial function is measured using near-infrared spectroscopy (NIRS) and markers of mitochondrial function from fasting blood samples at baseline and 24 weeks 5. Inflammatory markers (CRP, hs-CRP) are measured using fasting blood samples at baseline and 24 weeks 6. Lipid (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides) and glucose (fasting plasma glucose, fasting plasma insulin, and hemoglobin A1c) metabolism markers are measured using fasting blood samples and oral glucose tolerance test at baseline and 24 weeks. 7. Metabolomics measured with nuclear magnetic resonance (MNR) from fasting blood samples at baseline and 24 weeks 8. Gut microbiota are measured from stool samples with techniques based on the 16S-rRNA gene sequencing and separately Short Chain Fatty Acids (SCFA) content is determined from stool samples at baseline and 24 weeks 9. Advanced glycation end products (AGE) are measured using the AGE reader as skin autofluorescence at baseline and 24 weeks. 10. Body composition (lean body mass, fat mass, fat%) is measured using bioimpedance and anthropometrics (height, weight, body mass index, waist and hip circumference) at baseline and 24 weeks 11. Muscle strength is measured using the grip strength test, the upper body dynamic strength test and the repetitive squat test for the lower body at baseline and 24 weeks 12. Physical performance is measured using a spiroergometry test (VO₂max, Pmax), a 6,1-meter walk test (normal and maximal walking speed) and a one-legged stance test (balance) at baseline and 24 weeks. 13. Sleep is measured using the ActiGraph wGT3X-BT-accelerometer at baseline, at the 8th week, at the 16th week and at the 24-week and using the Oura-ring at baseline, during the whole 24-week intervention and at 24 weeks 14. Physical activity is measured using the ActiGraph wGT3X-BT-accelerometer at baseline, at the 8th week, at the 16th week and at the 24-week and using the Oura-ring at baseline, during the whole 24-week intervention and at the 24-week. Leisure-time physical activity is also measured using an exercise diary and Polar Vantage M multisport watch during the whole 24-week intervention. 15. Health-related quality of life (HRQoL) is measured using the 36-Item Short Form Survey (SF-36) at baseline and 24 weeks 16. Depressive symptoms are measured using the Beck Depression Inventory (BDI) at baseline and 24 weeks
Completion date	31/12/2025

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	50 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	150
Key inclusion criteria	1. Non-smoker or quit smoking ≥1 year ago 2. Age 50–70 years 3. Body mass index ≥25 and <32 kg/m² 4. Passed medical examination to participate 5. Not following a regular physical exercise regime or having a physically active lifestyle 6. Finnish or Swedish as a first language
Key exclusion criteria	1. Pre-existing, or history of major cardiovascular disease (coronary artery disease, heart failure, stroke, peripheral vascular disease) 2. Type 1 diabetes 3. Type 2 diabetes 4. Cancer 5. Neurodegenerative disease (e.g. Alzheimer’s disease, Parkinson’s disease) 6. Rheumatoid arthritis 7. Chronic obstructive pulmonary disease (COPD) 8. Diagnosed moderate or severe depression 9. Use of metformin or other hyperglycemia medication 10. Scheduled to undergo major surgery in the next 6 months 11. Findings detected during spiroergometry that limit safe participation to the intervention according to the Finnish national guidelines
Date of first enrolment	01/08/2022
Date of final enrolment	01/04/2025

Locations

Countries of recruitment

Finland

Study participating centre

Samfundet Folkhälsan i svenska Finland r.f.

Topeliuksenkatu 20
Helsinki
00250
Finland

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated and analysed during the current study will be available upon request from Niko Wasenius (niko.wasenius@helsinki.fi). Data will be shared in the EU/EEA region according to the general data protection regulations, Finnish national data protection act (1050/2018) and the act on the secondary use of health and social data (552/2019). Data will become available after the data collection has ended and the data has been cleaned and processed. Third-party usage requires a legal contract between the register holder and the third party. Data will be shared only for the original purpose of the study.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

03/10/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/07/2024 to 01/04/2025.
2. The overall end date was changed from 31/12/2024 to 31/12/2025.
3. The intention to publish date was changed from 01/08/2025 to 01/08/2026.
4. The plain English summary was updated to reflect these changes.
16/06/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/06/2022 to 01/08/2022.
2. The trial website has been added.
04/05/2022: The secondary outcome measures were updated.
22/04/2022: Trial's existence confirmed by the Ethics Committee of the Helsinki and Uusimaa Hospital District.