Ignite Creation Date:
2024-07-17 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06496204
Status:
COMPLETED
Last Update Posted:
2024-07-11
First Post:
2024-05-27
Brief Title:
Swedish Physical Activity and Fitness Longitudinal Study
Sponsor:
Karolinska Institutet
Organization:
Karolinska Institutet
Study Overview
Official Title:
A Longitudinal Approach to Characterize Loss of Muscle Mass and Function in Aging Humans - the Importance of Peripheral Nerve Integrity
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SPAF
Brief Summary:
Aging means loss of strength which can affect the ability to lead an active life and be independent Physical activity can counteract the loss of strength to some extent but individual differences are large and the mechanisms are partly unknown The hypothesis is that changes in the innervation and composition of the muscle may explain the individual differences in strength loss A group of Swedish men and women have participated in this study of physical performance for almost 50 years since they were 16 years old The project will improve the understanding of muscle aging The findings may help to develop strategies to counteract muscle loss and enable healthy aging and to promote physical activity throughout life
Detailed Description:
STUDY MATERIALS The investigators have finished the latest data collection performed at age 63 in 2021-2022 of the human longitudinal cohort study SPAF-1958 At baseline in 1974 six geographic areas in Sweden were systematically selected In each area one upper secondary school was randomly selected from which 429 224 male and 205 female pupils in the lowest grade level were randomly selected to be included in the study The entire cohort was invited for questionnaire and testing at age 16 34 and 52 and 63 years DATA COLLECTION Questionnaire The questionnaire included questions about lifestyle factors such as physical activity dietary habits smoking alcohol consumption
The questionnaire also included questions about health disease medication and personal traits Testing of physical performance Some tests for physical performance were used at all data collections from 16 to 63 years including aerobic capacity and muscle static and dynamic strength Specific tests assessing muscle function in relation to muscle weakness were added to the testing at 63 years Venous blood was drawn for analysis of standard health variables as well as extended studying of endocrine profile and inflammatory cell profile The muscle size of two selected muscles on the leg were estimated by ultrasound Body composition and muscle size were determined in 60 subjects by MR imaging of the whole body Testing of neurological status Motor nerve conductions studies NCS were performed on the right median and ulnar and bilaterally on tibial and peroneal nerves Sensory NCS were performed on the right median ulnar and superficial radial nerves and bilaterally on the sural and superficial peroneal nerves Motor and sensory conduction velocities proximal and distal compound muscle action potentials CMAP and sensory nerve action potentials SNAP were recorded For motor unit number estimation MUNE m tibialis anterior TA and m abductor policies brevis ABP were tested by electrical stimulation of the median and peroneal nerve respectively MUNE was obtained by dividing the size of the maximal CMAP by the size of the mean surface-recorded single motor unit potential S-MUP MUNEMax CMAP area Mean SMUP area To define small fibre neuropathy a skin biopsy was collected to measure the density of small fibre epidermal innervation Skeletal muscle samples were obtained with a Bergström biopsy needle from m vastus lateralis and were snap-frozen in liquid nitrogen cooled isopentane and stored at -80C To maximize the possibility to include high number of neuromuscular transmission junctions endplates in the muscle biopsy the optimal biopsy site was determined by location of maximal twitch response to electrical nerve stimulation Furthermore the needle was re-directed after penetration of the skin to cut myofibers as longitudinally as possible This approach was chosen to optimize the conditions for analyses of the NMJ
ANALYSES OF SKELETAL MUSCLE The data collection at 63 years will be completed with morphological and immune-enzyme-histochemical analysis of 120 muscle biopsies Disruption of axon and motor unit integrity may initiate and drive the wasting and functional impairment of skeletal muscles during aging To test our hypothesis of the neurogenic impact on loss of muscle strength the investigators will examine and compare biopsies of skeletal muscle from age 27 and 63 in the same individuals This part of the analyses will focus on fibre type transitions myosin subtypes change in fibre-size and clustering of fibre types with advancing age a sign of denervation followed by re-innervation For the biopsies at age 63 after cryo-sectioning muscle sections will be stained using enzyme histochemistry histological stains and immunohistochemistry followed by confocal microscopy imaging From 27 years of age there are sectioned and stained muscle tissue available from a subgroup of the cohort to compare with the characteristics of the muscle at 63 years These samples need to be digitalised in our microscopy and imaging analysis facility before analyses of fibre clustering Also the muscle biopsies harvested at age 63 will be analysed for NMJ by staining for acetylcholine presynaptic CHARNs postsynaptic receptors terminal Schwann cells and the parallel autonomic innervation norepinephrine The investigators will use a panel of antibodies including markers of axonal and terminal Schwann cell involvement in re-innervation The cryo-sectioning and refinementvalidation of the labelling protocols will be performed by HR in collaboration with BU TG and MW HR has a full-time position in the group and is specialized in these methods In addition the investigators apply for funding 1 month for a research assistant to digitalise and analyse muscle fibre composition from age 27 ANALYSES OF MAGNETIC RESONANCE IMAGES Subjects have been scanned with a 15 Tesla Siemens camera at Karolinska University Hospital in Huddinge The investigators used a modified 2-point Dixon fat-water sequence that scans the entire body in 6 minutes Automatic image analysis will be performed using AMRA segmentation software Advanced MR Analytics AB Linköping Sweden The data provided include adipose and muscle tissue of the entire body from neck to knee muscle volume and muscle fat infiltration in the anterior and posterior thigh muscles and subcutaneous adipose tissue in the abdomen and fat content of the liver The advantage of the results of the MRI technique is not only the very high reproducibility but also the fact that it can be adjusted to body size using muscle-specific z-scores for volume and fat infiltration This has been a major problem in the past as essentially small people were much more easily classified as sarcopenic while overweightobese people were rarely classified as having too little muscle mass The standardized z-score has been calculated for different age groups based on over 10 000 people scanned in the UK Biobank Both muscle volume value and fat infiltration of muscle were associated with physical function with the strongest predictive value when low muscle volume was combined with high fat infiltration ie adverse muscle composition
The questionnaire also included questions about health disease medication and personal traits Testing of physical performance Some tests for physical performance were used at all data collections from 16 to 63 years including aerobic capacity and muscle static and dynamic strength Specific tests assessing muscle function in relation to muscle weakness were added to the testing at 63 years Venous blood was drawn for analysis of standard health variables as well as extended studying of endocrine profile and inflammatory cell profile The muscle size of two selected muscles on the leg were estimated by ultrasound Body composition and muscle size were determined in 60 subjects by MR imaging of the whole body Testing of neurological status Motor nerve conductions studies NCS were performed on the right median and ulnar and bilaterally on tibial and peroneal nerves Sensory NCS were performed on the right median ulnar and superficial radial nerves and bilaterally on the sural and superficial peroneal nerves Motor and sensory conduction velocities proximal and distal compound muscle action potentials CMAP and sensory nerve action potentials SNAP were recorded For motor unit number estimation MUNE m tibialis anterior TA and m abductor policies brevis ABP were tested by electrical stimulation of the median and peroneal nerve respectively MUNE was obtained by dividing the size of the maximal CMAP by the size of the mean surface-recorded single motor unit potential S-MUP MUNEMax CMAP area Mean SMUP area To define small fibre neuropathy a skin biopsy was collected to measure the density of small fibre epidermal innervation Skeletal muscle samples were obtained with a Bergström biopsy needle from m vastus lateralis and were snap-frozen in liquid nitrogen cooled isopentane and stored at -80C To maximize the possibility to include high number of neuromuscular transmission junctions endplates in the muscle biopsy the optimal biopsy site was determined by location of maximal twitch response to electrical nerve stimulation Furthermore the needle was re-directed after penetration of the skin to cut myofibers as longitudinally as possible This approach was chosen to optimize the conditions for analyses of the NMJ
ANALYSES OF SKELETAL MUSCLE The data collection at 63 years will be completed with morphological and immune-enzyme-histochemical analysis of 120 muscle biopsies Disruption of axon and motor unit integrity may initiate and drive the wasting and functional impairment of skeletal muscles during aging To test our hypothesis of the neurogenic impact on loss of muscle strength the investigators will examine and compare biopsies of skeletal muscle from age 27 and 63 in the same individuals This part of the analyses will focus on fibre type transitions myosin subtypes change in fibre-size and clustering of fibre types with advancing age a sign of denervation followed by re-innervation For the biopsies at age 63 after cryo-sectioning muscle sections will be stained using enzyme histochemistry histological stains and immunohistochemistry followed by confocal microscopy imaging From 27 years of age there are sectioned and stained muscle tissue available from a subgroup of the cohort to compare with the characteristics of the muscle at 63 years These samples need to be digitalised in our microscopy and imaging analysis facility before analyses of fibre clustering Also the muscle biopsies harvested at age 63 will be analysed for NMJ by staining for acetylcholine presynaptic CHARNs postsynaptic receptors terminal Schwann cells and the parallel autonomic innervation norepinephrine The investigators will use a panel of antibodies including markers of axonal and terminal Schwann cell involvement in re-innervation The cryo-sectioning and refinementvalidation of the labelling protocols will be performed by HR in collaboration with BU TG and MW HR has a full-time position in the group and is specialized in these methods In addition the investigators apply for funding 1 month for a research assistant to digitalise and analyse muscle fibre composition from age 27 ANALYSES OF MAGNETIC RESONANCE IMAGES Subjects have been scanned with a 15 Tesla Siemens camera at Karolinska University Hospital in Huddinge The investigators used a modified 2-point Dixon fat-water sequence that scans the entire body in 6 minutes Automatic image analysis will be performed using AMRA segmentation software Advanced MR Analytics AB Linköping Sweden The data provided include adipose and muscle tissue of the entire body from neck to knee muscle volume and muscle fat infiltration in the anterior and posterior thigh muscles and subcutaneous adipose tissue in the abdomen and fat content of the liver The advantage of the results of the MRI technique is not only the very high reproducibility but also the fact that it can be adjusted to body size using muscle-specific z-scores for volume and fat infiltration This has been a major problem in the past as essentially small people were much more easily classified as sarcopenic while overweightobese people were rarely classified as having too little muscle mass The standardized z-score has been calculated for different age groups based on over 10 000 people scanned in the UK Biobank Both muscle volume value and fat infiltration of muscle were associated with physical function with the strongest predictive value when low muscle volume was combined with high fat infiltration ie adverse muscle composition
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| DNR 4-3972021 | OTHER_GRANT | None | None |
| DNR 4-25372023 | OTHER_GRANT | None | None |
| P2023-0054 | OTHER_GRANT | None | None |
| P2024-0076 | OTHER_GRANT | None | None |