High genetic running capacity promotes efficient metabolism with aging

Press release:

High running capacity is associated with health and longevity. However, whether high genetic running capacity promotes more efficient metabolism with aging is not known. A new study conducted in collaboration between the universities of Shanghai Jiao Tong University (China) and Jyväskylä (Finland) investigated the effects of genetic running capacity and aging on tissue metabolism. The study reveals that adipose tissue may have a key role in healthy aging.

Running capacity, expressed as aerobic capacity, refers to an individual’s capacity to utilize oxygen and is known to decrease with age, thereby affecting the whole body metabolism and health.

“We currently lack the information whether high genetic aerobic capacity promotes healthier metabolism in different tissues as we age,” explains Academy of Finland postdoctoral researcher Sira Karvinen from the Faculty of Sport and Health Sciences, University of Jyväskylä, Finland.

To study the question, animal models of high-capacity runners (HCR) and low-capacity runners (LCR) were utilized. These rodent lines differ in their aerobic capacity genetically. Samples of serum, muscle and adipose tissue were harvested from young and aged animals to explore the tissue metabolites.

“According to our results, high genetic running capacity was associated with more efficient amino acid metabolism in skeletal muscle. Inefficient amino acid metabolism is linked to increased adiposity and risk of metabolic diseases,” says Karvinen.

High genetic running capacity and aging interactively affected lipid metabolism in muscle and adipose tissue, possibly contributing to healthier metabolism with aging.

The results suggest that adipose tissue may have a more significant role in promoting healthy aging than previously thought. According to the current literature, around 50% of an individual’s aerobic capacity is genetically inherited and the other 50% can be gained via physical activity.

“Regular exercise promotes health whether you have genetically high or low aerobic capacity. Hence, it is highly recommended to promote one’s metabolism with exercise especially at older age, when aerobic capacity as well as other health parameters decline,” says the principal investigator, Professor Heikki Kainulainen from the Faculty of Sport and Health Sciences, University of Jyväskylä, Finland.

New research may explain why some people derive more benefits from exercise than others

Press release:

Although everyone can benefit from exercise, the mechanistic links between physical fitness and overall health are not fully understood, nor are the reasons why the same exercise can have different effects in different people. Now a study published in Nature Metabolism led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides insights related to these unanswered questions. The results could be helpful for determining the specific types of exercise most likely to benefit a particular individual and for identifying new therapeutic targets for diseases related to metabolism.

“While groups as a whole benefit from exercise, the variability in responses between any two individuals undergoing the very same exercise regimen is actually quite striking. For example, some may experience improved endurance while others will see improved blood sugar levels,” said senior corresponding author Robert E. Gerszten, MD, Chief of the Division of Cardiovascular Medicine at BIDMC. “To date, no aspects of an individual’s baseline clinical profile allow us to predict beforehand who is most likely to derive a significant cardiorespiratory fitness benefit from exercise training.”

To uncover the details behind exercise’s effects on the body and how these might differ from one person to the next, the team, including first author Jeremy Robbins, MD, of the Division of Cardiovascular Medicine at BIDMC, measured the blood levels of approximately 5,000 proteins in 650 sedentary adults before and after a 20-week endurance exercise program.

“We were particularly interested at looking at proteins in the blood to study the effects of exercise because there is a growing body of evidence showing that exercise stimulates the secretion of chemicals into circulation that can impart their effects on distant organs,” Robbins said.

A set of 147 proteins in the blood indicated an individual’s cardiorespiratory fitness, or VO2max, at the start of the study. Another set of 102 proteins indicated an individual’s change in VO2max following the completion of the exercise program.

“We identified proteins that emanate from bone, muscle, and blood vessels that are strongly related to cardiorespiratory fitness and had never been previously associated with exercise training responses,” said Gerszten, who is also the Herman Dana Professor of Medicine at Harvard Medical School and a Senior Associate Member of the Broad Institute of MIT and Harvard.

Robbins added, “Even though prior studies have shown that an individual’s baseline fitness level is unrelated to their response to exercise training, it was fascinating to see that there was minimal overlap between the protein profiles of baseline VO2max and its response to the exercise training intervention.”

With this information, the research team developed a protein score that improved their ability to predict an individual’s trainability, or change in VO2max. For example, the score identified individuals who were unable to significantly improve their cardiorespiratory fitness despite participating in the standardized exercise program. “Baseline levels of several proteins predicted who would respond to the exercise training protocol far better than any of our established patient factors,” Gerszten said.

In a separate community-based study, though part of the same paper, the scientists found that some of these proteins were linked to an elevated risk of early death, highlighting the link between cardiorespiratory fitness and long-term health outcomes.

“We now have a detailed list of new blood compounds that further inform our understanding of the biology of fitness and exercise adaptation, and predict individual responses to a given exercise regimen,” said Gerszten, who is also the Director of the Program in Personal Genomics and Cardiometabolic Disease at BIDMC. “While no pill is ever likely to recapitulate the diversity of benefits from exercise, our study has helped create a roadmap to further explore potential interventions and provides an important step in individualizing exercise as a therapy.” He noted that additional research is needed to expand the study’s findings to larger populations and to further refine the precise effects of the different proteins before and after exercise.