Mendelian randomization supports causality between overweight status and accelerated aging

Abstract

It is reported that overweight may lead to accelerated aging. However, there is still a lack of evidence on the causal effect of overweight and aging. We collected genetic variants associated with overweight, age proxy indicators (telomere length, frailty index and facial aging), etc., from genome‐wide association studies datasets. Then we performed MR analyses to explore associations between overweight and age proxy indicators. MR analyses were primarily conducted using the inverse variance weighted method, followed by various sensitivity and validation analyses. MR analyses indicated that there were significant associations of overweight on telomere length, frailty index, and facial aging (β = −0.018, 95% CI = −0.033 to −0.003, p = 0.0162; β = 0.055, 95% CI = 0.030–0.079, p < 0.0001; β = 0.029, 95% CI = 0.013–0.046, p = 0.0005 respectively). Overweight also had a significant negative causality with longevity expectancy (90th survival percentile, β = −0.220, 95% CI = −0.323 to −0.118, p < 0.0001; 99th survival percentile, β = −0.389, 95% CI = −0.652 to −0.126, p = 0.0038). Moreover, the findings tend to favor causal links between body fat mass/body fat percentage on aging proxy indicators, but not body fat‐free mass. This study provides evidence of the causality between overweight and accelerated aging (telomere length decreased, frailty index increased, facial aging increased) and lower longevity expectancy. Accordingly, the potential significance of weight control and treatment of overweight in combating accelerated aging need to be emphasized.

Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study

“…Therefore, this study aims to comprehensively explore the potential relationships between biological aging and neurodegenerative diseases as well as neurological tumors by integrating multiple biological age proxy indicators ( Yu et al, 2020 ; Duan et al, 2022 ; Chen et al, 2023 ). These indicators include molecular biomarkers such as TL and DNA methylation epigenetic age acceleration and phenotypic biomarkers such as frailty index and facial visual aging.…”

Physical activity, sedentary behavior, and the risk of frailty and falling: A Mendelian randomization study

“…in PA and minimizing sedentary time are linked to decreased weight gain and body fat, while overweight is associated with an increased risk of frailty and falls. [53][54][55] Given that body fat is likely involved in the causal pathway linking PA, sedentary behavior, and frailty and falling, it is challenging to disentangle independent effects of PA and sedentary behavior on the development of frailty and falling from adiposity. The close association between adiposity, PA, and sedentary behavior could be attributed to the fact that certain genetic instruments used to measure PA and LST have also demonstrated associations with genotypes associated with body fat.…”

“…Engaging in PA and minimizing sedentary time are linked to decreased weight gain and body fat, while overweight is associated with an increased risk of frailty and falls 53–55 . Given that body fat is likely involved in the causal pathway linking PA, sedentary behavior, and frailty and falling, it is challenging to disentangle independent effects of PA and sedentary behavior on the development of frailty and falling from adiposity.…”

The causal effects of atopic dermatitis on the risk of skin cancers: A two‐sample Mendelian randomization study

“…The F-statistics was applied to quantify the statistical power of IVs and can be calculated by the following formula: 23,24 An F-statistic of <10 indicates that the genetic variants used are weak IVs, which may lead to some bias to the MR estimates. 25 Thus, SNPs with an F-statistic of <10 are removed.…”