Energizing Mitochondria to Prevent Mobility Loss in Aging: Rationale and Hypotheses

Tian, Qu; Lee, Philip R.; Walker, Keenan A.; Ferrucci, Luigi

doi:10.1249/jes.0000000000000315

Cited by 14 publications

(9 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms underlying a connection between mitochondrial function and AD pathologic changes have been proposed, such as excessive ROS production and pro-inflammatory response. 30 cytes and promoting a pro-inflammatory phenotype. 31,32 Impaired mitophagy may also lead to disrupted synaptic homeostasis, which is likely to be one of the earliest AD pathological changes.…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration

Tian,

Bilgel,

Walker

et al. 2023

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

INTRODUCTIONMitochondrial dysfunction is implicated in the pathophysiology of many chronic diseases. Whether it is related to cognitive impairment and pathological markers is unknown.METHODSWe examined the associations of in vivo skeletal muscle mitochondrial function (post‐exercise recovery rate of phosphocreatine [kPCr] via magnetic resonance [MR] spectroscopy with future mild cognitive impairment (MCI) or dementia, and with positron emission tomography (PET) and blood biomarkers of Alzheimer's disease [AD] and neurodegeneration (i.e., Pittsburgh Compound‐B [PiB] distribution volume ratio [DVR] for amyloid beta [Aβ], flortaucipir (FTP) standardized uptake value ratio [SUVR] for tau, Aβ42/40 ratio, phosphorylated tau 181 [p‐tau181], neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]).RESULTSAfter covariate adjustment, each standard deviation (SD) higher kPCr level was associated with 52% lower hazards of developing MCI/dementia, and with 59% lower odds of being PiB positive with specific associations in DVR of frontal, parietal, and temporal regions, and cingulate cortex and pallidum. Higher kPCr level was also associated with lower plasma GFAP.DISCUSSIONIn aging, mitochondrial dysfunction may play a vital role in AD pathological changes and neuroinflammation.Highlights Higher in vivo mitochondrial function is related to lower risk of mild cognitive impairment (MCI)/dementia. Higher in vivo mitochondrial function is related to lower amyloid tracer uptake. Higher in vivo mitochondrial function is related to lower plasma neuroinflammation. Mitochondrial dysfunction may play a key role in Alzheimer's disease (AD) and neurodegeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration

Tian,

Bilgel,

Walker

et al. 2023

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our data emphasize the relevance of muscle mitochondrial energetics to aging health and further support aging mitochondria as a therapeutic target. 33,53 The impact of multimorbidity on healthcare systems and older adults is apparent in the tremendous costs of different disease combinations 54,55 and the loss of health-span in aging populations. 56 Developing a singular therapy targeting mitochondrial function that could improve multiple diseases at once would require more in-depth investigations of how muscle mitochondrial bioenergetic capacities are related to different chronic conditions.…”

Section: Discussionmentioning

confidence: 99%

Muscle mitochondrial bioenergetic capacities is associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA)

Mau,

Blackwell,

Cawthon

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundThe geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.MethodsThe Study of Muscle, Mobility and Aging (SOMMA) assessedex vivomuscle mitochondrial energetics in 764 older adults (mean age =76.4, 56.5% women, 85.9% non-Hispanic white) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95%CI]) for the likelihood of greater multimorbidity (four levels: 0 conditions, N=332; 1 condition, N=299; 2 conditions, N=98; or 3+ conditions, N=35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions.ResultsLower oxidative phosphorylation supported by fatty acids and/or complex-I and -II linked carbohydrates (e.g., Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR=1.32[1.13,1.54]) and separately with diabetes mellitus (OR=1.62[1.26,2.09]), depressive symptoms (OR=1.45[1.04,2.00]) and possibly chronic kidney disease (OR=1.57[0.98,2.52]) but not significantly with other conditions (e.g., cardiac arrhythmia, chronic obstructive pulmonary disease).ConclusionsLower muscle mitochondrial bioenergetic capacities was associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and is more strongly related to some conditions than others.(Words= 233)

show abstract

“…Mitochondrial energetics are known to decline with age, differ by sex and are strongly associated with slower gait speed and impaired physical function. 11,21,22 Furthermore, greater perceived physical fatigability, a known prognostic indicator of mobility decline, is more prevalent in women than men. 5,6,9 Thus, characterizing sex differences in the association between skeletal muscle energetics and perceived physical fatigability in a large cohort of older adults could provide novel insight into the potential role that mitochondrial energetics may play in aging and mobility decline (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in the Association between Skeletal Muscle Energetics and Perceived Physical Fatigability: The Study of Muscle, Mobility and Aging (SOMMA)

Gay,

Coen,

Harrison

et al. 2024

Preprint

View full text Add to dashboard Cite

Greater perceived physical fatigability and lower skeletal muscle energetics are predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher=greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N=873) were 76.3 ± 5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo) were associated with lower perceived physical fatigability, all p<0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS Physical ≥25, RPE Fatigability ≥12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p<0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the in vivo measures (p<0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.

show abstract

Energizing Mitochondria to Prevent Mobility Loss in Aging: Rationale and Hypotheses

Abstract: Mitochondria energetics and mobility.

Cited by 14 publications

References 54 publications

Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration

Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration

Muscle mitochondrial bioenergetic capacities is associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA)

Sex Differences in the Association between Skeletal Muscle Energetics and Perceived Physical Fatigability: The Study of Muscle, Mobility and Aging (SOMMA)

Contact Info

Product

Resources

About