Background: DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results: Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δ_age) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δ_age and mortality. A 5-year higher Δ_age is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δ_age. A pedigree-based heritability analysis of Δ_age was conducted in a separate cohort. The heritability of Δ_age was 0.43. Conclusions: DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.

Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates and test longevity or rejuvenating interventions. Here, we discuss key challenges to understand clock mechanisms and biomarker utility. This requires dissecting the drivers and regulators of age-related changes in single-cell, tissue- and disease-specific models, as well as exploring other epigenomic marks, longitudinal and diverse population studies, and non-human models. We also highlight important ethical issues in forensic age determination and predicting the trajectory of biological aging in an individual.

Purpose of review Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals. Recent findings In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, and methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, and TCA), air pollutants (particulate matter, black carbon, and benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, and dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modifications and microRNA. Summary For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed individuals develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally.

Air pollution has wide-ranging and deleterious effects on human health and is a major issue for the global community. The Global Burden of Disease study has described the worldwide impact of air pollution with as many as 3.1 million of 52.8 million all-cause and all-age deaths being attributable to ambient air pollution in the year 2010.¹ Moreover, ambient air pollution ranked ninth among the modifiable disease risk factors, being listed above other commonly recognized factors, such as low physical activity, a high-sodium diet, high cholesterol, and drug use. Finally, air pollution accounts for 3.1% of global disability-adjusted life years, an index that measures the time spent in states of reduced health.¹

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health‐based air‐quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution‐derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.

Objectives: We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome. Methods: We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction–pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter ≤ 2.5 μm [PM2.5], or sulfate) in multiple time windows (4 h to 7 d) before the examination. We estimated standardized regression coefficients (β) expressing the fraction of a standard deviation change in DNA methylation associated with a standard deviation increase in exposure. Measurements and Main Results: Repetitive element DNA methylation varied in association with time-related variables, such as day of the week and season. LINE-1 methylation decreased after recent exposure to higher black carbon (β = −0.11; 95% confidence interval [CI], −0.18 to −0.04; P = 0.002) and PM2.5 (β = −0.13; 95% CI, −0.19 to −0.06; P < 0.001 for the 7-d moving average). In two-pollutant models, only black carbon, a tracer of traffic particles, was significantly associated with LINE-1 methylation (β = −0.09; 95% CI, −0.17 to −0.01; P = 0.03). No association was found with Alu methylation (P > 0.12). Conclusions: We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined. Rationale: Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis.