The effects of aging on platelet bioenergetics

Background: In a rapidly aging population, functional decline is a considerable public health burden. Studies suggest that increased fatigue has a negative impact on function. Additionally, diminished mitochondrial function associated with aging has been associated with higher fatigue. Platelets represent a minimally invasive source of mitochondria in which bioenergetic profiles can be measured. Identification of bioenergetic dysfunction associated with aging could elucidate novel biomarkers or targets and lead to interventions aimed at ameliorating the public health burden of functional decline. Methods: As part of the Health Aging and Body Composition (Health ABC) study, venous blood and muscle biopsy samples from the vastus lateralis were taken from a subset of the cohort to measure bioenergetics. The Health ABC participants also completed a 400m long-distance corridor walk and fatigability questionnaire. We compared the Health ABC participants (n=32, 88±2 yrs) to a race, gender and body mass index matched younger cohort (n=32, 26±5 yrs) to identify differences in platelet bioenergetics that could be attributed to aging. Results: Older adults showed 228.2 ± 20.39 pmolO2/min/5x107platelets maximal respiration and 39.15 ± 2.849 pmolO2/min/5x107platelets proton leak, both significantly higher (p=0.0492; p=0.0446) than in younger adults (177.4 ± 15.01 pmolO2/min/5x107platelets maximal respiration; 31.48 ± 2.39 pmolO2/min/5x107platelets proton leak). We also observed significantly lower (p=0.0496) baseline oxygen consumption rates in older adults (107.4 ± 5.294 pmolO2/min/5x107platelets) compared with younger (123.6 ± 6.083 pmolO2/min/5x107platelets). Amongst older adults, platelet glycolytic rate did not significantly correlate with LDCW time (p=0.2213), however there was a significant positive correlation (r=0.398; p=0.0359), between basal glycolytic rate and fatigability. Additionally, significant correlations were evident in older adults between non-ATP linked respiration in platelets and muscle state 4 respiration (r=0.489, p=0.0178) and in maximal respiration between platelets and muscle (r=0.444, p=0.034). Discussion: These data demonstrate that systemic alterations in bioenergetics experienced by aged adults could contribute to fatigability and subsequent functional decline. Additionally, platelets can function as a surrogate measure of mitochondrial function in lieu of more invasive procedures. Future studies will elucidate possible racial disparities in bioenergetics and the specific mechanisms underlying the age-associated differences in bioenergetics. This work could lead to potential interventions aimed at attenuating the public heath burden of functional decline in older adults.