Associations between medium- and long-term exposure to air temperature and epigenetic age acceleration

Abstract

Climate change poses a serious threat to human health worldwide, while aging populations increase. However, no study has ever investigated the effects of air temperature on epigenetic age acceleration. This study involved 1,725 and 1,877 participants from the population-based KORA F4 (2006-2008) and follow-up FF4 (2013-2014) studies, respectively, conducted in Augsburg, Germany. The difference between epigenetic age and chronological age was referred to as epigenetic age acceleration and reflected by Horvath's epigenetic age acceleration (HorvathAA), Hannum's epigenetic age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Epigenetic Skin and Blood Age acceleration (SkinBloodAA). Daily air temperature was estimated using hybrid spatiotemporal regression-based models. To explore the medium- and long-term effects of air temperature modeled in time and space on epigenetic age acceleration, we applied generalized estimating equations (GEE) with distributed lag non-linear models, and GEE, respectively. We found that high temperature exposure based on the 8-week moving average air temperature (97.5th percentile of temperature compared to median temperature) was associated with increased HorvathAA, HannumAA, GrimAA, and SkinBloodAA: 1.83 (95% CI: 0.29-3.37), 11.71 (95% CI: 8.91-14.50), 2.26 (95% CI: 1.03-3.50), and 5.02 (95% CI: 3.42-6.63) years, respectively. Additionally, we found consistent results with high temperature exposure based on the 4-week moving average air temperature was associated with increased HannumAA, GrimAA, and SkinBloodAA: 9.18 (95% CI: 6.60-11.76), 1.78 (95% CI: 0.66-2.90), and 4.07 (95% CI: 2.56-5.57) years, respectively. For the spatial variation in annual average temperature, a 1 °C increase was associated with an increase in all five measures of epigenetic age acceleration (HorvathAA: 0.41 [95% CI: 0.24-0.57], HannumAA: 2.24 [95% CI: 1.95-2.53], PhenoAA: 0.32 [95% CI: 0.05-0.60], GrimAA: 0.24 [95%: 0.11-0.37], and SkinBloodAA: 1.17 [95% CI: 1.00-1.35] years). In conclusion, our results provide first evidence that medium- and long-term exposures to high air temperature affect increases in epigenetic age acceleration.

Keywords: Air temperature; Epigenetic age acceleration; Medium- and long-term effects; Spatial and temporal variation.

Fig. 1.. Medium-term effects of 4- and 8-weeks moving average of air temperature on epigenetic age acceleration.

Note: Low temperature: effects of low temperature exposure, 2.5th percentile of temperature compared to median temperature. High temperature: effects of high temperature exposure, 97.5th percentile of temperature compared to median temperature. The median temperature was 9.7 °C; 2.5th percentile of temperature was 1.5 °C and 1.4 °C for 4-week and 8-week moving averages of temperature, respectively; 97.5th percentile of temperature was 18.5 °C and 18.3 °C for 4-week and 8-week moving averages of temperature, respectively. HorvathAA: Horvath’s epigenetic age acceleration. HannumAA: Hannum’s epigenetic age acceleration. PhenoAA: PhenoAge acceleration. GrimAA: GrimAge acceleration. SkinBloodAA: Epigenetic Skin and Blood Age acceleration.

Fig. 2.. Long-term effects of annual average temperature per 1 °C increase on epigenetic age acceleration.

Note: HorvathAA: Horvath’s epigenetic age acceleration. HannumAA: Hannum’s epigenetic age acceleration. PhenoAA: PhenoAge acceleration. GrimAA: GrimAge acceleration. SkinBloodAA: Epigenetic Skin and Blood Age acceleration.

Fig. 3.. Long-term effects of annual average temperature per 1 °C increase on epigenetic age acceleration modified by sex, obesity, cardiovascular disease, and diabetes.

Note: Red error bars show significantly different effect estimates between subgroups (P-value for the interaction term < 0.05). HorvathAA: Horvath’s epigenetic age acceleration. HannumAA: Hannum’s epigenetic age acceleration. PhenoAA: PhenoAge acceleration. GrimAA: GrimAge acceleration. SkinBloodAA: Epigenetic Skin and Blood Age acceleration.