The Gao Xu/Huang Jing/Wu Shaowei/Zhang Ling team found that short-term PM2.5 exposure accelerates epigenetic age based on DNA methylation

September 27, 2022, Environmental Science & Technology (IF: 11.
357), an authoritative journal in the field of environmental science The research results of Associate Professors Gao Xu and Huang Jing of the School of Public Health of Peking University, Professor Wu Shaowei of the School of Public Health of Xi'an Jiaotong University and Professor Zhang Ling of the School of Public Health of Capital Medical University were published online, and the paper entitled "Short-term Exposure of PM_2.
5 and Epigenetic Aging: A" was published Quasi-Experimental Study (Short-term exposure to PM_2.
5 and epigenetic aging: a quasi-experimental study, https://pubs.
acs.
org/doi/full/10.
1021/acs.
est.
2c05534 ）
。 The study conducted repeated health examinations on 2 6 healthy adults before, during and after several atmospheric PM_2.
5 pollution events (PPW) in Beijing from 2017 to 2018.
Biological samples were obtained and a series of biomarkers were tested in the laboratory, and 7 epigenetic ages were calculated based on methylation levels at multiple sites in the DNA methylation profile It is used to reflect the level of aging, and to investigate whether the aging effect of PM_2.
5 is mediated by related mechanisms
by measuring a variety of coagulation markers, oxidative stress markers and inflammatory factors.
Short-term PM_2.
5 exposure has been found to mediate the increase in epigenetic age in humans through the
above biological mechanisms.

Epigenetic age is a DNA methylation-based biological marker of aging that has been found to predict aging-related disease risk
.
Although China's average annual air pollution level has dropped significantly in recent years, short-term air pollution events still occur from time to time and may accelerate population aging
.
Until now, the relationship between short-term (< 1 week) exposure to PM _2.
5 and epigenetic age has been poorly understood, so this study aimed to explore PM _2.
5 Whether short-term PM _2.
5 exposure changes based on DNA methylation when a contamination event occurs naturally Epigenetic age
.
In addition, since coagulation, oxidative stress and systemic inflammation may be potential mechanisms for PM _2.
5 to accelerate human aging, the study also explored whether changes in some related markers can mediate PM _2.
5 Effects
on epigenetic age.

The study recruited 32 healthy volunteers (26 of whom completed the entire study and included them in the analysis) from Peking University students to obtain the atmosphere from the Air Quality Index website (http://aqicn.
org/city/beijing/).
The air quality forecast information of the PM _2.
5 pollution incident is several days before and after the pollution event, and the volunteers are subjected to repeated health examinations
at 3 time points before, during and after the pollution event.
PM_2.
5 was tested in indoor and outdoor places of volunteer activities, and the time of exposure window 0-24 hours and 24-48 hours before each health check was calculated to weighted individual PM _2.
5 Exposure level
.

Figure 1 Study design flowchart

The study first evaluated the three phases before, during and after the occurrence of P M 2.
5 contamination events 7 epigenetic ages [AA (Horvath), AA (Hannum), AA （PhenoAge）、AA（GrimAge）、DunedinPoAm、MS and epiTOC] indicators
.
Seven epigenetic ages were normalized (z-scored) to unify data scales for different algorithms
.
The association between changes in epigenetic age (Δ EAs) and time-weighted individual PM 2.
5 exposure concentrations was then analyzed by a mixed linear regression model.

After that, an intermediary analysis was carried out to explore whether the association between PM _2.
5 and epigenetic age was caused by liquid blood markers, Mediated
by changes in levels of markers of oxidative stress or inflammatory factors.

The results showed that individual PM2.
5 exposure from 0 to 24 hours before health examination was significantly associated
with six epigenetic ages.
Individual _PM2.
5 exposure increases by 10μg/m3 (0-24h).
，AA (Horvath)、AA (Hannum)、AA (GrimAge)、DunedinPoAm、MS and epiTOC z-score changes increased by 0.
035, 0.
035, and 0.
050, respectively , 0.
055, 0.
052, and 0.
037.

24-48 hours individual PM_2.
5 exposure concentration is weakly
associated with all epigenetic ages.
where the PM_2.
5 concentration increases by 10μg/^m3 (24-48h) The z-score change for AA (GrimAge), DunedinPoAm, and MS increased by only 0.
030, respectively , 0.
048, and 0.
033 (P<0.
05).

Table 1 Individual _PM2.
5 exposure levels and 7 at 0-24 hours and 24-48 hours Correlation of epigenetic age of species

The study further found that individual PM_2.
5 exposure was associated with AA (GrimAge), DunedinPoAm, and MS The association between the changes was mainly mediated by changes in extracellular superoxide dismutase (EC-SOD) (mediated ratio of 12.
8% ~ 28.
1%), and partly through soluble CD40 The change of ligand (sCD40L) was mediated (mediated ratio of 0.
6% ~ 10.
7%)
.
Other biomarkers including sP-selectin, 8-isoPGF2α, MDC, and MIP-1β can also mediate partial effects (Mediated ratio>5%)
.

Fig.
2 Distribution of mediating effects of coagulation, oxidative stress and systemic inflammatory pathways

The results of this study suggest that short-term PM_2.
5 exposure accelerates aging reflected by DNA methylation profiles through coagulation, oxidative stress and systemic inflammatory pathways.
Caution is still needed to pay attention to the adverse health effects
of short-term exposure to air pollution.

Associate Professors Gao Xu and Huang Jing are the co-first authors of this paper, and Professor Wu Shaowei and Professor Zhang Ling are the co-corresponding authors
of this paper.
This study was supported by the National Key Research and Development Program of China (2017YFC0211601, 2016YFC0900603, 2016YFC0207103), the National Natural Science Foundation of China (82073509), and the Natural Science Foundation of Beijing Municipality 7192098), the Beijing Key Laboratory of Environmental Toxicology Open Project and the Peking University Health Science Center Scientific Research Start-up Fund (BMU2021YJ044) and other projects
.

(School of Public Health, Peking University)