Platelet bioenergetics correlate with muscle energetics and are altered in older adults

Abstract

P-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 31 P-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.

Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement

“…Blood cells contain fully functional mitochondria, and are abundant, self-renewing, and minimally invasive to obtain. Our group and others have successfully employed Seahorse XF and/or Oroboros to circulating cells to demonstrate that this methodology is feasible [ 43 , 44 ], reproducible in human populations [ 40 ], and that bioenergetics of circulating cells reflect bioenergetics in solid tissues such as the heart [ 42 ], skeletal muscle [ 42 , 45 ], brain [ 46 ], and lungs [ 47 ]. Further, these studies demonstrate alterations in blood cell bioenergetics in a number of natural biological conditions (e.g aging) or pathologies, and correlate with physical or clinical parameters of these conditions [ 45 , [47] , [48] , [49] ].…”

“…Our group and others have successfully employed Seahorse XF and/or Oroboros to circulating cells to demonstrate that this methodology is feasible [ 43 , 44 ], reproducible in human populations [ 40 ], and that bioenergetics of circulating cells reflect bioenergetics in solid tissues such as the heart [ 42 ], skeletal muscle [ 42 , 45 ], brain [ 46 ], and lungs [ 47 ]. Further, these studies demonstrate alterations in blood cell bioenergetics in a number of natural biological conditions (e.g aging) or pathologies, and correlate with physical or clinical parameters of these conditions [ 45 , [47] , [48] , [49] ]. Altered platelet bioenergetics have been measured in neurologic [ 46 ], metabolic [ 46 ], hematologic [ 44 ], cardiopulmonary [ 47 , 49 , 50 ], and infectious diseases [ 51 ] ( Fig.…”

“…Bioenergetic profiles have been measured in platelets isolated from patients with a wide array of diagnosed diseases. This figure demonstrates published platelet bioenergetic alterations in neurologic disease including Alzheimer's disease [ 53 ] and bipolar disorder [ 54 ], metabolic changes including type II diabetes [ 55 ] and advanced age [ 45 ], cardiopulmonary diseases including pulmonary hypertension [ 50 , 56 ] and asthma [ 47 , 57 ], sickle cell disease as a hematologic disease [ 44 ], and infectious disease such as sepsis [ 58 ]. …”

Effects of Ultramarathon Running on Mitochondrial Function of Platelets and Oxidative Stress Parameters: A Pilot Study

“…PLTs have been suggested to reflect the systemic effects of exercise on multi-organ systems based on existing data on the release of different cytokines, ions, metabolites and tricarboxylic acid (TCA) cycle intermediates from contracting muscles to the blood stream (primarily span-2 metabolites: succinate, malate, and fumarate), which are further affecting succinate receptor 1 (SUCNR1) positive cells such as PLTs in a dose-dependent manner (Gibala et al, 1998;Lewis et al, 2010;Högberg et al, 2011;Ariza et al, 2012;Knechtle and Nikolaidis, 2018). Moreover, recent studies have demonstrated parallels between oxidative respiration of skeletal muscle mitochondria and those of PLTs (Tyrrell et al, 2016;Braganza et al, 2019;Rose et al, 2019). Thus, the well accepted association between cardiorespiratory fitness and OXPHOS capacity of skeletal muscles (Walsh et al, 2001;Daussin et al, 2008;Pesta et al, 2011;Jacobs and Lundby, 2013;Christensen et al, 2016) might also apply (at least partly) to PLT mitochondrial function (Tyrrell et al, 2016).…”

Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity

“…In the past decade, peripheral blood platelets have been increasingly used as a source of viable mitochondria to investigate cellular respiratory dysfunction in order to complement studies reporting organ-related mitochondrial dysfunction in various pathologies [ 14 ]. Due to the low invasiveness through which they are obtained (especially as compared to muscle cells), platelets are an attractive source of human mitochondria for studies of toxic effects elicited by statin exposure [ 15 , 16 ].…”