Grip strength is inversely associated with DNA methylation age acceleration

Peterson, Mark D.; Collins, Stacey D.; Meier, Helen; Brahmsteadt, Alexander; Faul, Jessica D.

doi:10.1002/jcsm.13110

Cited by 20 publications

(12 citation statements)

References 42 publications

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“…Lower mDNAge in muscle appears to be a feature of the molecular environment with exercise adaptation that could have practical consequences for biological ageing and muscle performance. Indeed, emerging evidence suggests that blood mDNAge inversely associates with grip strength and frailty in ageing humans (Peterson et al., 2022; Verschoor et al., 2021) and is lower following a dietary/physical activity intervention in postmenopausal women (Fiorito et al., 2021). Exercise training and OKSM share substantial gene expression overlap.…”

Section: Discussionmentioning

confidence: 99%

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

Jones

Dimet²,

Haghani

et al. 2023

The Journal of Physiology

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Exercise promotes functional improvements in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown. Using transcriptome profiling from (1) a skeletal muscle‐specific in vivo Oct3/4, Klf4, Sox2 and Myc (OKSM) reprogramming‐factor expression murine model; (2) an in vivo inducible muscle‐specific Myc induction murine model; (3) a translatable high‐volume hypertrophic exercise training approach in aged mice; and (4) human exercise muscle biopsies, we collectively defined exercise‐induced genes that are common to partial reprogramming. Late‐life exercise training lowered murine DNA methylation age according to several contemporary muscle‐specific clocks. A comparison of the murine soleus transcriptome after late‐life exercise training to the soleus transcriptome after OKSM induction revealed an overlapping signature that included higher JunB and Sun1. Also, within this signature, downregulation of specific mitochondrial and muscle‐enriched genes was conserved in skeletal muscle of long‐term exercise‐trained humans; among these was muscle‐specific Abra/Stars. Myc is the OKSM factor most induced by exercise in muscle and was elevated following exercise training in aged mice. A pulse of MYC rewired the global soleus muscle methylome, and the transcriptome after a MYC pulse partially recapitulated OKSM induction. A common signature also emerged in the murine MYC‐controlled and exercise adaptation transcriptomes, including lower muscle‐specific Melusin and reactive oxygen species‐associated Romo1. With Myc, OKSM and exercise training in mice, as well habitual exercise in humans, the complex I accessory subunit Ndufb11 was lower; low Ndufb11 is linked to longevity in rodents. Collectively, exercise shares similarities with genetic in vivo partial reprogramming. Key points Advances in the last decade related to cellular epigenetic reprogramming (e.g. DNA methylome remodelling) toward a pluripotent state via the Yamanaka transcription factors Oct3/4, Klf4, Sox2 and Myc (OKSM) provide a window into potential mechanisms for combatting the deleterious effects of cellular ageing. Using global gene expression analysis, we compared the effects of in vivo OKSM‐mediated partial reprogramming in skeletal muscle fibres of mice to the effects of late‐life murine exercise training in muscle. Myc is the Yamanaka factor most induced by exercise in skeletal muscle, and so we compared the MYC‐controlled transcriptome in muscle to Yamanaka factor‐mediated and exercise adaptation mRNA landscapes in mice and humans. A single pulse of MYC is sufficient to remodel the muscle methylome. We identify partial reprogramming‐associated genes that are innately altered by exercise training and conserved in humans, and propose that MYC contributes to some of these responses.

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Section: Discussionmentioning

confidence: 99%

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

Jones

Dimet²,

Haghani

et al. 2023

The Journal of Physiology

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“…As our moderated-mediation results suggest, biological age-related declines in strength occurred in males and females suggesting that HGS could be used as a proxy measure of accelerated aging, providing that we acknowledge sex as a biological variable and consider this in methodological designs. Previous research examining strength performance as a standalone variable, however, has either provided no association with epigenetic aging ( McCrory et al, 2020 ), or demonstrated an association in females only ( Peterson et al, 2021 ). Previously, a stronger association between HGS and impaired activities of daily living has been observed in men than women ( Oksuzyan et al, 2010 ).…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, evidence favors DNAmGrimAge estimates of biological aging as the most predictive “clock” for physical performance, whereby reductions in physical function are associated with an older epigenome ( Lu et al, 2019 ; McCrory et al, 2020 ; Peterson et al, 2022a ). However, the limited available data examining associations of epigenetic age specifically with HGS indicate no association ( McCrory et al, 2020 ), or an association in females only ( Peterson et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Pain interference mediates the association between epigenetic aging and grip strength in middle to older aged males and females with chronic pain

Peterson

Crow

Johnson

et al. 2023

Front. Aging Neurosci.

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IntroductionChronic pain is one of the leading causes of disability that may accelerate biological aging and reduce physical function. Epigenetic clocks provide an estimate of how the system ages and can predict health outcomes such as physical function. Physical function declines may be attributed to decreases in muscle quality due to disuse that can be measured quickly and noninvasively using grip strength. The purpose of this study was to explore the associations among self-reported pain, grip strength, and epigenetic aging in those with chronic pain.MethodsParticipants (57.91 ± 8.04 years) completed pain questionnaires, a blood draw and hand grip strength task. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), and used the subsequent difference of predicted epigenetic age from chronological age (DNAmGrimAge-Difference).ResultsExploratory pathway analyses revealed that pain intensity mediated the association between DNAmGrimAge-difference and handgrip strength in males only (β = −0.1115; CI [−0.2929, −0.0008]) and pain interference mediated the association between DNAmGrimAge-difference and handgrip strength in males β = −0.1401; CI [−0.3400, −0.0222]), and females (β = −0.024; CI [−0.2918, −0.0020]).DiscussionChronic knee pain may accelerate epigenetic aging processes that may influence handgrip strength in older age adults. Chronic pain could be a symptom of the aging body thus contributing to declines in musculoskeletal function in later life.

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“…32 Grip strength dynamometers are easy to use, provide more precise measurement than the alternative manual muscle testing, and have established psychometric properties in nearly all conditions. 33,34 Two important features of these successful measurement RT are their adaptability to different populations and their relative advantage over prior gold standard measures of the vitals and strength domains. 31 Developers are likely to succeed by enhancing precision in current clinical metrics, instead of expending resources on the creation of novel measurement criteria.…”

Section: Rehabilitation Technology Characteristicsmentioning

confidence: 99%

Uncovering clinical rehabilitation technology trends: field observations, mixed methods analysis, and data visualization

Celian,

Redd,

Smaller

et al. 2024

Preprint

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Objective: To analyze real-world rehabilitation technology (RT) use, with a view toward enhancing RT development and adoption. Design: A convergent, mixed-methods study using direct field observations, semi-structured templates, and summative content analysis. Setting: Ten neurorehabilitation units in a single health system. Participants: 3 research clinicians (1OT, 2PTs) observed ~60 OTs and 70 PTs in inpatient; ~18 OTs and 30 PTs in outpatient. Interventions: Not applicable Main Outcome Measures: Characteristics of RT, time spent setting up and using RT, and clinician behaviors. Results: 90 distinct devices across 15 different focus areas were inventoried. 329 RT-uses were documented over 44 hours with 42% of inventoried devices used. RT was used more during interventions (72%) than measurement (28%). Intervention devices used frequently were balance/gait (39%), strength/endurance (30%), and transfer/mobility training (16%). Measurement devices were frequently used to measure vitals (83%), followed by grip strength (7%), and upper extremity function (5%). Device characteristics were predominately AC-powered (56%), actuated (57%), monitor-less (53%), multi-use (68%), and required little familiarization (57%). Set-up times were brief (mean = 3.8 and 0.8 for intervention and measurement, respectively); more time was spent with intervention RT (25.6) than measurement RT (7.3). RT nearly always involved verbal instructions (72%) with clinicians providing more feedback on performance (59.7%) than on results (30%). Therapists' attention was split evenly between direct attention towards the patient during clinician treatment (49.7%) and completing other tasks such as documentation (50%). Conclusions: Even in a tech-friendly hospital, majority of available RT were observed un-used, but identifying these usage patterns is crucial to predict eventual adoption of new designs from earlier stages of RT development. An interactive data visualization page supplement is provided to facilitate this study.

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Grip strength is inversely associated with DNA methylation age acceleration

Cited by 20 publications

References 42 publications

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

Pain interference mediates the association between epigenetic aging and grip strength in middle to older aged males and females with chronic pain

Uncovering clinical rehabilitation technology trends: field observations, mixed methods analysis, and data visualization

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