RNA Sequencing of Whole Blood Defines the Signature of High Intensity Exercise at Altitude in Elite Speed Skaters

Abstract

Although high altitude training has been increasingly popular among endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. Seven elite female speed skaters were profiled on the 18th day of high-altitude adaptation. Whole blood RNA-seq before and after an intense 1 h skating bout was used to measure gene expression changes associated with exercise. In order to identify the genes specifically regulated at high altitudes, we have leveraged the data from eight previously published microarray datasets studying blood expression changes after exercise at sea level. Using cell type-specific signatures, we were able to deconvolute changes of cell type abundance from individual gene expression changes. Among these were PHOSPHO1, with a known role in erythropoiesis, and MARC1 with a role in endogenic NO metabolism. We find that platelet and erythrocyte counts uniquely respond to altitude exercise, while changes in neutrophils represent a more generic marker of intense exercise. Publicly available data from both single cell atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for the dynamic evaluation of physiological changes in an athlete’s body.

Whole blood transcriptome characterization of young female triathlon athletes following an endurance exercise: a pilot study

“…A 24-h long resting period almost completely reversed the gene activation pattern generated by exercise load. These observations together with the results of a recent study ( 22 ) suggest that whole blood RNA-seq is a useful tool for monitoring physiological effects of various exercise programs, albeit further studies are needed to confirm this assertion. Application of ImSig set of immune cell gene signatures helps to investigate immune cell type-specific gene expression changes associated with the response to endurance exercise.…”

“…These observations are consistent with the results of a recent study. Glotov et al ( 22 ) applied whole blood RNA-seq to seven elite female skaters, to assess the immunological and metabolic effects of high-altitude adaptation. They found that inflammatory and immune pathways dominated the observed changes, and on a cellular level, neutrophil degranulation accounts for a substantial fraction of upregulated genes.…”

“…They found that inflammatory and immune pathways dominated the observed changes, and on a cellular level, neutrophil degranulation accounts for a substantial fraction of upregulated genes. The majority of pathways enriched among the downregulated genes were related to ribosomal proteins and other components of transcriptional and translational machinery ( 22 ). Despite different exercise loads applied, the consistency of our results with the gene expression data of this another study ( 22 ) suggests that whole blood RNA-seq is a useful tool for monitoring physiological effects of various exercise loads.…”

Effects of LHTH Training at 1600 m on Exercise Performance, Complete Blood Count and Erythropoietin: A Case Study of South Korean Elite Male Cross-Country Skiers

“…Although there have been previous studies that the number of WBC decreased as a result of LHTH training, it is generally reported that the activation of white blood cells is increased by excessive exercise and high-intensity training rather than the effect of altitude [80][81][82]. Platelets play an important role in blood coagulation and hemostasis and living at altitude and vigorous exercise can increase the number of platelets, and excessive increase in the number of platelets can increase bleeding tendency or cause thromboembolism [83,84]. Conversely, acute high-altitude exposure may decrease platelets but return to normal with a compensatory effect after short-term adaptation [85,86].…”

The emerging roles of PHOSPHO1 and its regulated phospholipid homeostasis in metabolic disorders

“…These results indicated a role for PHOSPHO1 in stress-related energy metabolism. The expression of PHOSPHO1 was increased in blood samples from athletes with high-altitude training and vigorous intensity exercise ( Glotov et al, 2022 ). Given that hypoxia causes stress erythropoiesis ( Wang et al, 2021 ), Whether PHOSPHO1 regulates energy metabolism in high-altitude adaptation-induced erythropoiesis remains to be explored.…”