Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals.
Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals.
复制标题
DOI：
10.1186/s13148-016-0301-7
复制
发表时间：
2017
影响因子：
5.7
通讯作者：
Hurme M
中科院分区：
文献类型：
--
作者：
Nevalainen T;Kananen L;Marttila S;Jylhävä J;Mononen N;Kähönen M;Raitakari OT;Hervonen A;Jylhä M;Lehtimäki T;Hurme M
人类衰老与主要表观遗传机制之一DNA甲基化的深刻变化有关。这些变化中的一些以类似时钟的方式发生，即，与个体的日历年龄相关，从而提供新的衰老生物标志物。一些报告已经确定了与表观遗传年龄加速有关的因素。然而，分析表观遗传年龄的时间变化也很重要，即，观察到的加速的持续时间，以及可能的治疗和生活方式改变的影响。为了解决这个问题，我们确定了一组183名健康个体的表观遗传年龄，使用的血液样本来自相隔25年的两个时间点（15-24岁和40-49岁之间）。此外，我们还确定了一个由90岁参与者组成的队列中119名个体的表观遗传年龄。这些通过使用基于353个CpG位点的甲基化水平的Horvath算法来确定。数据表示为表观遗传年龄与日历年龄的偏差（日历年龄减去表观遗传年龄= Δ年龄，ΔAGE）。由于肥胖通常与加速衰老和退行性表型相关，因此在以下三个年龄组中分析了体重指数（BMI）与ΔAGE的相关性：年轻人，中年人和九十岁人。数据显示，BMI与ΔAGE降低相关，即，中年个体的表观遗传年龄增加。这种影响也出现在从成年早期到中年的25年期间，其中BMI的增加与ΔAGE的降低显著相关。我们还分析了年轻人和老年人的BMI和表观遗传年龄之间的关联，但这些关联并不显著。总的来说，这份报告的主要发现表明，可以观察到BMI增加与中年人血细胞加速表观遗传衰老之间的关联，如果BMI在成年期增加，这种影响也是可以检测到的。BMI和表观遗传年龄之间的关联只能在中年组中观察到，这一事实并不排除这种关联可能存在于整个人类寿命中的可能性;它可能只是被年轻人和90岁个体中的混杂因素所掩盖。本文的在线版本（doi：10.1186/s13148-016-0301-7）包含补充材料，可供授权用户使用。
Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications. To address this issue, we determined the epigenetic age for a cohort of 183 healthy individuals using blood samples derived from two time points that were 25 years apart (between 15–24 and 40–49 years of age). Additionally, we also determined the epigenetic ages of 119 individuals in a cohort consisting of 90-year-old participants (nonagenarians). These were determined by using the Horvath algorithm based on the methylation level of 353 CpG sites. The data are indicated as the deviation of the epigenetic age from the calendar age (calendar age minus epigenetic age = delta age, ΔAGE). As obesity is often associated with accelerating aging and degenerative phenotypes, the correlation of the body mass index (BMI) with the ΔAGE was analyzed in the following three age groups: young adults, middle-aged, and nonagenarian. The data showed that BMI is associated with decreased ΔAGE, i.e., increased epigenetic age, in middle-aged individuals. This effect is also seen during the 25-year period from early adulthood to middle age, in which an increase in the BMI is significantly associated with a decrease in the ΔAGE. We also analyzed the association between BMI and epigenetic age in young and elderly individuals, but these associations were not significant. Taken together, the main finding on this report suggests that association between increased BMI and accelerated epigenetic aging in the blood cells of middle-aged individuals can be observed, and this effect is also detectable if the BMI has increased in adulthood. The fact that the association between BMI and epigenetic age can only be observed in the middle-aged group does not exclude the possibility that this association could be present throughout the human lifespan; it might just be masked by confounding factors in young adults and nonagenarian individuals. The online version of this article (doi:10.1186/s13148-016-0301-7) contains supplementary material, which is available to authorized users.