Abstract
BACKGROUND Physical function decreases with age, and though bioenergetic alterations contribute to this decline, the mechanisms by which mitochondrial function changes with age remain unclear. This is partially because human mitochondrial studies require invasive procedures, such as muscle biopsies, to obtain live tissue with functional mitochondria. However, recent studies demonstrate that blood cells are potentially informative in identifying systemic bioenergetic changes. Here, we hypothesize that human platelet bioenergetics reflect bioenergetics measured in muscle biopsies.METHODS Bioenergetics were measured in platelets isolated from younger (18–35 years) and older (86–93 years) adults by extracellular flux analysis. Muscle biopsy respirometry and noninvasive 31P-MRS were also performed in older adults.RESULTS Maximal and ATP-linked respiratory rate measured in platelets from older adults correlated significantly with muscle maximal respiration (r = 0.595; P = 0.003) and maximal ATP production (r = 0.643; P = 0.004; by 31P-MRS) in the same individuals. Comparison of platelet bioenergetics in older and younger adults showed lower basal and ATP-linked respiration in older adults. Platelets from older adults also showed enhanced proton leak, which was due to increased protein levels of uncoupling protein 2, and correlated with gate speed (r = 0.58; P = 0.0019). While no significant difference in glycolysis was observed in older compared to younger adults, platelet glycolytic rate correlated with fatigability (r = 0.44; P = 0.016).CONCLUSION These data advance the mechanistic understanding of age-related changes in mitochondrial function. Further, they suggest that measuring platelet bioenergetics provides a potential supplement or surrogate for muscle biopsy measurement and may be a valuable tool to study mitochondria in age-related decline of physical function.FUNDING NIH grants T32HL110849 and 1R01HL133003-01A1, NIH Career Development Award K01 AG044437, the Hemophilia Center of Western Pennsylvania, and University Pittsburgh Medical Center Stimulating Pittsburgh Research in Geroscience.
Authors
Andrea Braganza, Catherine G. Corey, Adam J. Santanasto, Giovanna Distefano, Paul M. Coen, Nancy W. Glynn, Seyed-Mehdi Nouraie, Bret H. Goodpaster, Anne B. Newman, Sruti Shiva
Figure 3
Platelet basal respiration is decreased and proton leak is increased in older adults.
