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EVIDENCE SUPPORTING THE UTILITY OF BLOOD CELL RESPIRATORY CAPACITY AS A SYSTEMIC MARKER OF MITOCHONDRIAL HEALTH AND BIOLOGICAL AGE

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title
EVIDENCE SUPPORTING THE UTILITY OF BLOOD CELL RESPIRATORY CAPACITY AS A SYSTEMIC MARKER OF MITOCHONDRIAL HEALTH AND BIOLOGICAL AGE
author
Tyrrell, Daniel John
abstract
The global population of older adults is projected to increase to over 2 billion by the year 2050, and although mitochondria are implicated in nearly all age-related diseases, currently there is no clinically useful measure of systemic mitochondrial health. Multiple lines of evidence suggest that blood cells may recapitulate mitochondrial function systemically, but there is a gap in the knowledge as to whether blood cell mitochondrial function reliably informs on mitochondrial function of other tissues or biological age in older adults. This project aims to develop a minimally invasive, objective measure of blood bioenergetic function that provides a reliable index of systemic mitochondrial health for aging and age-related diseases. We tested the hypotheses that blood cell bioenergetic function is reliable, correlates with bioenergetics of other metabolically active tissues, relates to indices of physical function in older adults, and responds to intervention. PBMC and platelet respiration produced similar respiratory rates over 1 week with intraclass correlation coefficients greater than 0.5. Platelet and monocyte bioenergetics associated with bioenergetics of skeletal and cardiac muscle, and PBMC bioenergetics correlated with gait speed, expanded short physical performance battery, leg strength, grip strength, and plasma interleukin-6 level in obese older adults. Interestingly, we found that PBMC respiration decreased significantly in response to resistance training and weight loss in obese older adults. Because weight loss is known to reduce resting metabolic rate, this may indicate that blood cell respiration tracks with systemic metabolic demand. Fat mass loss correlated with greater reduction of maximal PBMC respiration and reserve respiratory capacity, and lower baseline respiration predicted greater fat loss. In conclusion, we discovered that circulating blood cell respiration is reproducible, is associated with bioenergetics in muscle tissue and physical function, and is altered by resistance training and weight loss intervention. This addresses considerable gaps in the knowledge regarding the clinical utility of blood cell respiratory capacity, revealing that circulating blood cell respirometry is related to key aspects of biological health in old age and may provide a minimally invasive index of systemic mitochondrial health for use in large-scale clinical trials and geriatric medicine.
subject
Bioenergetics
Biological Age
Blood cells
Cellular Respiration
Metabolism
Mitochondria
contributor
Molina, Anthony J (committee chair)
Files, Daniel C (committee member)
Nicklas, Barbara J (committee member)
Register, Thomas (committee member)
Craft, Suzanne (committee member)
date
2017-01-14T09:35:31Z (accessioned)
2019-01-13T09:30:10Z (available)
2016 (issued)
degree
Physiology and Pharmacology (discipline)
embargo
2019-01-13 (terms)
identifier
http://hdl.handle.net/10339/64195 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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