Effects of walking on epigenetic age acceleration: a Mendelian randomization study

#1

Abstract

Introduction

Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA).

Methods

We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran’s Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy.

Results

The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = − 1.84, 95% CI (− 2.94, − 0.75)), PhenoAge (BETA = − 1.57, 95% CI (− 3.05, − 0.08)), Horvath (BETA = − 1.09 (− 2.14, − 0.04)), and Hannum (BETA = − 1.63, 95% CI (− 2.70, − 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05).

Conclusion

Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.

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#2

I don’t believe it, unless they show where the genes are expressed, subject to confounding, or in a satisfactory way explain why it is not confounded. Clear mechanism of action helps.

(Obesity MR IIRC is in the brain, which might be confounded by educational attainment or something).

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#3

I believe that this is unproven BS.

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#4

The question that I ask is – which is cause & which effect? Do people walk faster because they are healthier or are they healthier because they walk faster?

I’ve noticed that people who aren’t very healthy walk slowly, but I’m reasonably sure that their less good health is not caused by their lack of speed at walking.

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#5

deceleration of the acceleration of all four classical epigenetic clocks acceleration

This is one of the most confusing sentences I’ve ever read. I still can’t tell if we’re accelerating or decelerating.

What about the rate of change of acceleration (the jerk!)?