Nevalainen Tapio, Kananen Laura, Marttila Saara, Jylhävä Juulia, Mononen Nina, Kähönen Mika, Raitakari Olli T, Hervonen Antti, Jylhä Marja, Lehtimäki Terho, Hurme Mikko
Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland.
Gerontology Research Center, Tampere, Finland.
Clin Epigenetics. 2017 Feb 14;9:20. doi: 10.1186/s13148-016-0301-7. eCollection 2017.
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.
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。其中一些变化以类似时钟的方式发生，即与个体的实际年龄相关，从而提供了一种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相关的因素。然而，分析表观遗传年龄的时间变化，即观察到的加速持续时间，以及可能的治疗和生活方式改变的影响也很重要。
为了解决这个问题，我们使用来自两个相隔25年的时间点（15 - 24岁和40 - 49岁）的血液样本，确定了183名健康个体队列的表观遗传年龄。此外，我们还确定了由90岁参与者（非agenarians）组成的队列中119名个体的表观遗传年龄。这些是通过使用基于353个CpG位点甲基化水平的Horvath算法确定的。数据表示为表观遗传年龄与实际年龄的偏差（实际年龄减去表观遗传年龄 = 年龄差，ΔAGE）。由于肥胖通常与衰老加速和退行性表型相关，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、中年人以及非agenarians。
数据表明，在中年个体中，BMI与ΔAGE降低相关，即表观遗传年龄增加。在从成年早期到中年的25年期间也观察到这种效应，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中BMI与表观遗传年龄之间的关联，但这些关联不显著。
综上所述，本报告的主要发现表明，在中年个体的血细胞中可以观察到BMI增加与表观遗传衰老加速之间的关联，并且如果成年期BMI增加，这种效应也可检测到。BMI与表观遗传年龄之间的关联仅在中年组中观察到这一事实并不排除这种关联可能在整个人类寿命中存在的可能性；它可能只是被年轻人和非agenarians个体中的混杂因素所掩盖。
