Longevity Briefs: 12 Weeks Of Exercise Leads To More ‘Youthful’ Blood Protein Levels

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Chronological age (how many years you’ve lived) doesn’t necessarily correspond to how “old” someone’s body is biologically. People of the same age can have very different risks of age-related disease and disability. Scientists are therefore seeking biomarkers of ageing – functional measurements, molecular readouts or other metrics that reflect ageing better than a calendar. One such biomarker is proteomic ageing: changes in patterns of circulating proteins in the blood, reflecting age-related changes in metabolism and immune function for example. In this study, which is in preprint and is awaiting full publication, researchers investigate how a supervised 12-week exercise regime affects proteomic ageing.

The discovery:

Researchers started by combing through data from over 45,000 participants (aged 56 on average) of the UK Biobank, a large anonymised health database from the UK. They looked at a proteomic ageing score called ProtAgeGap, which is essentially the difference between someone’s predicted age based on proteomic measurements and their chronological age. A positive ProtAgeGap (meaning proteomic age is higher than chronological age) could suggest more rapid ageing, while a negative value could suggest the opposite. Researchers found that a higher ProtAgeGap was correlated with lower levels of physical activity and a greater risk of developing type 2 diabetes. This increased risk of type 2 diabetes wasn’t fully explained by physical activity – people with high physical activity levels were still more at risk of diabetes if their ProtAgeGap was high.

Researchers then conducted a controlled exercise trial to test whether physical activity could change participants’ proteomic ageing score. This consisted of a 12-week supervised exercise intervention in 13 normal weight and 13 overweight sedentary men, with an average age of 50 and 53 respectively. Participants completed an exercise program involving a total of 2 hours of supervised endurance cycling and 2 hours of supervised strength training per week, and had blood proteins measured before and after. The intervention produced a modest but measurable reduction in ProtAgeGap, roughly equivalent to reversing 10 months of proteomic ageing. One protein that showed a particularly large change was CLEC14A, which increased significantly following exercise. This protein is involved in the formation and function of blood vessels and was also found to correlate with sensitivity to the blood sugar-lowering hormone insulin. Changes were similar between the normal weight and overweight groups.

In addition to measuring protein levels, the team also studied changes in gene expression in skeletal muscle and adipose (fat) tissue. They found changes consistent with improved function of mitochondria (which produce ATP, the ‘cellular fuel’ necessary for muscle contraction and many other processes) and signaling changes in fat suggesting better metabolic function.

The implications:

Given the well established benefits of exercise on metabolic health, it’s not surprising that putting sedentary people through a relatively intense exercise program has a beneficial effect on their proteome. Does making someone’s proteome look like that of someone 10 months younger really equate to a reversal of ageing? It certainly can’t be a bad thing. In many ways the more interesting part of this study is the identification of specific proteins that are particularly responsive to exercise, like CLEC14A. In the future, it may be more efficient to focus on tracking these key proteins as markers of proteomic health, and perhaps explore whether they can be targeted to replicate some of the benefits of exercise.

It’s interesting that the effects in normal and overweight participants were similar. This could indicate that sedentary people have just as much to gain from exercise in terms of proteomic ageing, regardless of weight. However, it could also simply mean that there weren’t enough participants to detect more subtle differences between the two groups. The study was also in men only, so we don’t know if women would respond in the same way. Furthermore, while proteomic changes may correlate with ageing, what we actually want to know is whether they translate into reduced incidence of age-related disease and death, and this study didn’t last long enough to answer that question. Another weakness of the study was that there was no non-exercising control group for the exercise intervention study. While it may seem unlikely that participants ProtAgeGap would have reversed due to anything other than the exercise (for example, improved mental health from social contact with the supervisors), it technically can’t be ruled out.