Scientists are looking for models of ageing to help determine the causes of many age-related diseases. By using Labradors, the researchers from the University of California have demonstrated a new model for ageing that can be applied to other mammalian species and provide insights into our own genome.

Over 100,000 people die each day from age-related causes and the mechanisms are poorly understood. The main factors implicated are cell death, DNA damage and DNA methylation. Whether these factors are part of development or due to our environment is up for debate.

Dogs provide a unique model opportunity as humans have bred over 450 distinct breeds, resulting in genetically homogenous groups that have few differences in their DNA – useful for investigating complex traits such as ageing. Dogs display similar life stages to humans and although the lifespan of breeds varies wildly – larger dogs living 10 fewer years than their smaller counterparts – they provide a useful resource for investigating the conservation of ageing.

DNA methylation involves the addition of a methyl group (CH3) to DNA at cytosine-guanine pairs – CpG dinucleotides. This doesn’t alter the underlying sequence but modifies its activity, most commonly repressing it. The proportion of the genome that is methylated changes over time, increasing as we age. The study of methylation has resulted in an ‘epigenetic clock’ that can be used to estimate the age of cells, tissues and organisms. By pinpointing where these changes occur in the genome and over what timescale, researchers can identify potential targets that lead to the slowing or even reversal of ageing.

104 Labrador Retrievers were compared to 320 human methylomes using Synteny Bisulphite Sequencing to determine if there was a relationship between age and methylation state. The data showed that dogs experience conserved methylation changes, like humans, and provided a formula for translating a dog’s age into human years: human_age = 16ln(dog_age) + 31.

The formula not only provides a fun fact but allows the physiological state of an individual to be quantitatively translated from one species to another, which was demonstrated with mice. This shows the epigenome can accurately reflect physiological state and poses the question as whether successfully altering it could modify the effects of ageing.

Rather than using rotations around the Sun, methylation levels can be used to accurately portray our age as altered by environment and disease – a more relevant marker for our health throughout our lives, admittedly not as easy to put on a card.

Megan Hickland

For further reading on Epigenetics, FLG’s Megan recommends The Epigenetics Revolution by Nessa Carey – a tour of what we know of epigenetics and the implications for ageing and cancer.

 

At the beginning of this century enormous progress had been made in genetics. The Human Genome Project finished sequencing human DNA. It seemed it was only a matter of time until we had all the answers to the secrets of life on this planet.

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