Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap
In Periodic Paralysis (PP), a rare inherited condition caused by mutation in skeletal muscle ion channels, the phenotype changes with age, transitioning from the episodic attacks of weakness that give the condition its name, to a more degenerative phenotype of permanent progressive weakness and myop...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1507485/full |
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| author | Karen Suetterlin Karen Suetterlin Sinead Law William David Arnold William David Arnold William David Arnold William David Arnold |
| author_facet | Karen Suetterlin Karen Suetterlin Sinead Law William David Arnold William David Arnold William David Arnold William David Arnold |
| author_sort | Karen Suetterlin |
| collection | DOAJ |
| description | In Periodic Paralysis (PP), a rare inherited condition caused by mutation in skeletal muscle ion channels, the phenotype changes with age, transitioning from the episodic attacks of weakness that give the condition its name, to a more degenerative phenotype of permanent progressive weakness and myopathy. This leads to disability and reduced quality of life. Neither the cause of this phenotype transition, nor why it occurs around the age of 40 is known. However, 40 is also the age of onset of ‘normal’ age-related physiological decline when we consider (a) muscle mass and strength (b) physical function at the world class level and (c) age-related mitochondrial dysfunction. Elevated Na+, mitochondrial dysfunction and sarcoplasmic Ca2+ leak via the skeletal muscle ryanodine receptor (RyR1) have been implicated in both periodic paralysis myopathy and skeletal muscle ageing. We suggest this combination may trigger a negative spiral ultimately leading to progressive muscle failure. Understanding the interaction between ageing physiology and disease phenotype will provide a window into the healthy ageing process but also help understand how, and why PP phenotype changes with age. Understanding the mechanism underlying PP phenotype-transition and its link with ageing physiology, not only has the potential to identify the first disease modifying therapies for PP, but also to identify novel and potentially tractable mechanisms that contribute to sarcopenia, the pathological loss of muscle mass and function with age. |
| format | Article |
| id | doaj-art-5709a4c4c3624e539de7d3ecad7916aa |
| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-5709a4c4c3624e539de7d3ecad7916aa2024-12-24T10:04:03ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-12-011510.3389/fneur.2024.15074851507485Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlapKaren Suetterlin0Karen Suetterlin1Sinead Law2William David Arnold3William David Arnold4William David Arnold5William David Arnold6AGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United KingdomThe John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, United KingdomAGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United KingdomNextGen Precision Health, University of Missouri, Columbia, MO, United StatesDepartment of Physical Medicine and Rehabilitation, University of Missouri, Columbia, MO, United StatesDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United StatesDepartment of Neurology, University of Missouri, Columbia, MO, United StatesIn Periodic Paralysis (PP), a rare inherited condition caused by mutation in skeletal muscle ion channels, the phenotype changes with age, transitioning from the episodic attacks of weakness that give the condition its name, to a more degenerative phenotype of permanent progressive weakness and myopathy. This leads to disability and reduced quality of life. Neither the cause of this phenotype transition, nor why it occurs around the age of 40 is known. However, 40 is also the age of onset of ‘normal’ age-related physiological decline when we consider (a) muscle mass and strength (b) physical function at the world class level and (c) age-related mitochondrial dysfunction. Elevated Na+, mitochondrial dysfunction and sarcoplasmic Ca2+ leak via the skeletal muscle ryanodine receptor (RyR1) have been implicated in both periodic paralysis myopathy and skeletal muscle ageing. We suggest this combination may trigger a negative spiral ultimately leading to progressive muscle failure. Understanding the interaction between ageing physiology and disease phenotype will provide a window into the healthy ageing process but also help understand how, and why PP phenotype changes with age. Understanding the mechanism underlying PP phenotype-transition and its link with ageing physiology, not only has the potential to identify the first disease modifying therapies for PP, but also to identify novel and potentially tractable mechanisms that contribute to sarcopenia, the pathological loss of muscle mass and function with age.https://www.frontiersin.org/articles/10.3389/fneur.2024.1507485/fullageingmyopathysarcopeniachannelopathylife coursemitochondria |
| spellingShingle | Karen Suetterlin Karen Suetterlin Sinead Law William David Arnold William David Arnold William David Arnold William David Arnold Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap Frontiers in Neurology ageing myopathy sarcopenia channelopathy life course mitochondria |
| title | Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap |
| title_full | Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap |
| title_fullStr | Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap |
| title_full_unstemmed | Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap |
| title_short | Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap |
| title_sort | periodic paralysis across the life course age related phenotype transition and sarcopenia overlap |
| topic | ageing myopathy sarcopenia channelopathy life course mitochondria |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1507485/full |
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