Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, UK.
Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, UK.
Geroscience. 2021 Oct;43(5):2363-2378. doi: 10.1007/s11357-021-00445-8. Epub 2021 Aug 31.
Human DNA methylation profiles have been used successfully to develop highly accurate biomarkers of aging ("epigenetic clocks"). Although these human epigenetic clocks are not immediately applicable to all species of the animal kingdom, the principles underpinning them appear to be conserved even in animals that are evolutionarily far removed from humans. This is exemplified by recent development of epigenetic clocks for mice and other mammalian species. Here, we describe epigenetic clocks for the domestic cat (Felis catus), based on methylation profiles of CpGs with flanking DNA sequences that are highly conserved between multiple mammalian species. Methylation levels of these CpGs are measured using a custom-designed Infinium array (HorvathMammalMethylChip40). From these, we present 3 epigenetic clocks for cats; of which, one applies only to blood samples from cats, while the remaining two dual-species human-cat clocks apply both to cats and humans. We demonstrate that these domestic cat clocks also lead to high age correlations in cheetahs, tigers, and lions. It is expected that these epigenetic clocks for cats possess the potential to be further developed for monitoring feline health as well as being used for identifying and validating anti-aging interventions.
人类 DNA 甲基化图谱已成功用于开发高度精确的衰老生物标志物(“表观遗传时钟”)。尽管这些人类表观遗传时钟不能立即应用于动物王国的所有物种,但支撑它们的原则似乎在与人类进化距离甚远的动物中也得到了保留。这方面的一个例子是最近为老鼠和其他哺乳动物物种开发的表观遗传时钟。在这里,我们描述了基于多个哺乳动物物种之间高度保守的侧翼 DNA 序列的 CpG 甲基化图谱的家猫(Felis catus)的表观遗传时钟。使用定制设计的 Infinium 阵列(HorvathMammalMethylChip40)测量这些 CpG 的甲基化水平。从中,我们为猫提出了 3 个表观遗传时钟;其中,一个仅适用于猫的血液样本,而其余两个人类-猫双物种时钟则同时适用于猫和人类。我们证明,这些家猫的时钟在猎豹、老虎和狮子中也能导致高年龄相关性。预计这些家猫的表观遗传时钟具有进一步开发用于监测猫的健康以及用于识别和验证抗衰老干预措施的潜力。