BackgroundEpigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.ResultsWe analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.ConclusionsEpigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1030-0) contains supplementary material, which is available to authorized users.

Do changes in neuronal structure underlie cortical plasticity? Here we used time-lapse two-photon microscopy of pyramidal neurons in layer 2/3 of developing rat barrel cortex to image the structural dynamics of dendritic spines and filopodia. We found that these protrusions were highly motile: spines and filopodia appeared, disappeared or changed shape over tens of minutes. To test whether sensory experience drives this motility we trimmed whiskers one to three days before imaging. Sensory deprivation markedly (approximately 40%) reduced protrusive motility in deprived regions of the barrel cortex during a critical period around postnatal days (P)11-13, but had no effect in younger (P8-10) or older (P14-16) animals. Unexpectedly, whisker trimming did not change the density, length or shape of spines and filopodia. However, sensory deprivation during the critical period degraded the tuning of layer 2/3 receptive fields. Thus sensory experience drives structural plasticity in dendrites, which may underlie the reorganization of neural circuits.

Lung cancer is considered an age-associated disease, whose progression is in part due to accumulation of genomic instability as well as age-related decline in system integrity and function. Thus even among individuals exposed to high levels of genotoxic carcinogens, such as those found in cigarette smoke, lung cancer susceptibility may vary as a function of individual differences in the rate of biological aging. We recently developed a highly accurate candidate biomarker of aging based on DNA methylation (DNAm) levels, which may prove useful in assessing risk of aging-related diseases, such as lung cancer. Using data on 2,029 females from the Women's Health Initiative, we examined whether baseline measures of “intrinsic epigenetic age acceleration” (IEAA) predicted subsequent lung cancer incidence. We observed 43 lung cancer cases over the nearly twenty years of follow-up. Results showed that standardized measures of IEAA were significantly associated with lung cancer incidence (HR: 1.50, P = 3.4×10−3). Furthermore, stratified Cox proportional hazard models suggested that the association may be even stronger among older individuals (70 years or above) or those who are current smokers. Overall, our results suggest that IEAA may be a useful biomarker for evaluating lung cancer susceptibility from a biological aging perspective.