With technical advancement came the opportunity and insight to combine age-related methylation changes of multiple DNA loci to develop a highly accurate age estimator for all human tissues. The significance and specificity of these alterations remained a source of speculation until the development of an array-based technology that permitted the simultaneous quantification of methylation levels of specific CpG positions on the human genome. It was known for a long while that the degree of cellular DNA methylation alters with age. Specifically, we present here DNA methylation-based biomarkers (epigenetic clocks) of age for blood from cats. Here, we aimed to develop and evaluate epigenetic clocks for cats, as such biomarkers are necessary for translating promising anti-aging interventions from humans to cats and vice versa, and to also provide the possibility of using the epigenetic aging rate of cats to inform on feline health for which, a quantitative measure is presently unavailable. This has instigated the development of similar clocks for other mammals such as mice and dogs. The human epigenetic clocks have already found many biomedical applications including the measure of biological age in human anti-aging clinical trials. While there is a rich literature on human epigenetic clocks for various individual and multiple tissues, we are not aware of any existing epigenetic clocks for cats.
A pre-requisite for such investigations, however, is a highly accurate set of biomarkers of aging for both, cats, and humans. Identification of environmental factors and living conditions that affect aging, as well as potential mitigation measures, can be achieved by proxy, with cats. These investigations, however, have yet to be extended to cats since these pets share similar environments and living conditions with their human owners as well. It has been recognized that domestic dogs fulfill these criteria. Ideally, testing should occur in species that are evolutionarily close to humans, similar in size, have high genetic diversity, and share the same environment as humans. Interventions to slow aging are being sought. Age is undoubtedly the biggest risk factor for a vast majority of diseases in animals, and cats are no exception. The maximum (confirmed) lifespan of cats is 30 years according to the animal age data base (anAge) but most cats succumb to diseases before they are 20 years old. Most owners of domestic cats lament the short lifespan of these widely popular pets. 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. We demonstrate that these domestic cat clocks also lead to high age correlations in cheetahs, tigers, and lions.
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. Methylation levels of these CpGs are measured using a custom-designed Infinium array (HorvathMammalMethylChip40). 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. This is exemplified by recent development of epigenetic clocks for mice and other mammalian species. 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. Human DNA methylation profiles have been used successfully to develop highly accurate biomarkers of aging (“epigenetic clocks”).
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