Predicting cognitive ageing by behavioural, neuronal, and genetic biomarkers
Our aim is to explore the cognitive ageing of family dogs in a complex way, using an interdisciplinary approach with the most advanced behavioural, neuroscientific and genetic testing methods. The results are expected to provide guidelines for a healthy lifestyle toward successful ageing, to pave the way for the development of therapies and preventive methods to increase canine welfare, and to aid our understanding of the biological background human cognitive ageing.
The project is funded by an ERC Starting Grant (EVOLOR-680040, 1/06/2016-31/05/2021, PI: Enikő Kubinyi)
- If you are or want to be a researcher, join us! PostDocs: write a proposal; PhD Candidates click here. BSc & MSc internships: write an email to Eniko Kubinyi: firstname.lastname@example.org
- If you have a methusaleh dog (older than 16 years above 20 kg or older than 20 years under 20 kg), please send us his/her DNA. You can easily collect DNA samples from your dog (see the pictures below). If you agree to provide your dog’s sample please follow these steps and ship the dried swabs together with the essential information about the dog (name, age, sex, breed, etc.) in an envelope to the following address: Eniko Kubinyi, Department of Ethology, Budapest, Pazmany Peter setany 1/C, 1117, Hungary
- To provide guidelines for a healthy lifestyle toward successful ageing.
- To pave the way for the development of therapies and preventive methods to increase canine welfare.
- To aid our understanding of the biological background of human cognitive ageing.
- Relying on a unique longitudinal behavioural investigation we describe the different trajectories of the ageing phenotype (e.g. healthy vs pathological). This could help veterinarians to recognise the symptoms early, and initiate necessary counter actions.
- Based on large scale, world-wide surveys we reveal specific environmental risk factors which facilitate and also protective factors which may postpone ageing
- We assess the contribution of candidate genes and other genetic markers to the variance of ageing.
- We aim to find specific set of fMRI and EEG related neural markers which are associated with cognitive test performance, and separate specific neural factors affecting performance from the potential influence of decreased sensory and motor functions.
Dogs’ mean life time is around 13 years, in specific breeds it ranges from 8 year to 14 years. We follow the life of dogs 2 years younger than the expected mean age of their breed and conduct regular physiological and behavioural (mostly with automatic data collection by e-collar, eye-tracking, touch screen) measures. This also allows comparing dogs that do not reach mean life span, and those which live longer.
We investigate with validated questionnaires and behavioural tests what factors (food calorie content, excessive weight, sex, sexual status, lifestyle, education, etc.) influence successful ageing or cognitive dysfunction. We want to explore whether personality traits contribute to the clinical symptoms of individuals with the same level of brain ageing. Subjects for further studies are selected on the basis of these tests, and grouped to successful and not successful ageing dogs.
We also apply functional magnetic resonance imaging (fMRI) tests on dogs trained for 6-8 minute-long motionless lying (a globally unique sample of dogs which happily participate in the fMRI occasions, see http://bit.ly/1F21ZHk). We will use fMRI for measuring brain activity during the processing of auditory and visual stimuli and to identify neural correlates (for example structural atrophy, decline of contralateral regions) which are associated with cognitive ageing.
In humans, the major cognitive domains, memory in particular, show high heritability, which is still functional in old age. Several candidate genes were tested for association with both cognitive ability in older people and cognitive decline during ageing. Currently we know very little about the genetic background of ageing in dogs. Our aim is to find associations between candidate genes and specific aging phenotypes.
We also apply cross-sectional studies when we compare young and old dogs by both behavioural tests and questionnaires, and screen them repeatedly. Analysis of these data would offer a robust insight about potential risk factors for aging and cognitive decline of dogs. We believe that this study also raises the owner’s awareness on dog aging, which may also improve the welfare of those dogs.
Staff (link to cvs&pics): principal investigator: Enikő Kubinyi, PhD (cv), researchers: Sára Sándor, Kálmán Czeibert, Lisa Wallis, Boglárka Erdélyi-Belle, PhD; students:Ivaylo Iotchev, Dóra Szabó, Flóra Szánthó; BSc&MSc students: Zsófia Bognár, Cecília Czibere, Renáta Böröczki, Bianka Stiegmann; research assistants: Borbála Győri, Rita Báji
Collaborative partners: Anna Kis, PhD; Borbála Turcsán, PhD; Márta Gácsi, PhD; Attila Andics, PhD; Prof. Ádám Miklósi
More about dog ageing
Almost one third of 11-12-year-old dogs and 70% of 15-16 year-old-dogs show cognitive disturbances corresponding to human senile dementia: spatial disorientation, social behaviour disorders (e.g. problems with recognizing family members), repetitive (stereotype) behaviour, apathy, increased irritability, sleep-wake cycle disruption, incontinence, and reduced ability to accomplish tasks. Pathological states of cognitive decline are an important research field, however in the Senior Family Dog Project we focus on non-pathological cognitive ageing, which affects each dog’s and their owner’s quality of life.
Senescence is a naturally occurring complex biological process, and it is one of the most relevant problems to understand how active and healthy ageing can be achieved. The study of dog ageing is significant from at least two applied perspectives. First, dogs’ increased life span is a direct consequence of sharing their life with humans. Despite the growing number of aged dogs in present day populations, very little is known about the actual prevalence and risk factors of age-related changes in dogs. The relative extended life span in dogs offered by the protective human environment artificially enhances the proportion of dogs with cognitive decline in the population which is a serious welfare concern. Research could facilitate the early recognition and treatment of certain conditions, as well as provide a way for a preventive and predictive approach. More appropriate life experiences (e.g. feeding, physical and mental exercises) could increase the chance of less detrimental ageing and improve dog welfare.
Second, dogs living in families provide a good natural model for human ageing. Dogs sharing their lives with humans gained considerably from this alliance by doubling their mean life span. As companion animals, the same environmental factors affect them as people (chemicals, air pollution, noise pollution, lack of exercise, etc.) which are suspected risk factors of cognitive decline in humans. They excel in displaying socio-cognitive skills in interaction with humans, in comparison to other species. Socio-cognitive aspects of ageing are very important for humans and here certain populations of dogs offer an unprecedented animal model.
The diversity of life span in dogs
The maximum life span of wolves in captivity may reach the age of 20 years. The maximum life span recorded for dogs is around 22-24 years. Thus wolves and dogs in general have similar maximum life span. However, most experts assume that the mean expected life span for wolves is between 5-7 years of age. In the case of purebred dogs mean life span may range from 5.5 to 14.5 years, for mixed-breed dogs the same value is 13.1 years. Even dog breeds, associated with shorter life expectancies reach the mean lifespan of wolves in nature. This means that dogs suffer to a much higher degree from cognitive decline in comparison to wolves because these age-classes generally do not survive in nature. This leads to a welfare issue in old dogs, as many of them live likely suffer from decrease in sensory and mental performance.
Main factors influencing the canine life span
The life span of dogs mainly depends on body size. The larger (70-80 kg) dogs live an average of 7-8 years, six years less than 10-20 kg do. The relative early death of large sized dogs was often referred to as an opposing trend to the observation on wild species in which large size predicts longer life span. Studying the relationship between size and ageing in other species showed that species level processes should be distinguished from within-species effects. While the positive correlation between body size and longevity exists for great taxonomic clades, within species smaller individuals live longer.
This means that dog breeds follow the trend which is characteristic for within species variability. Similar observations have been also provided for domesticated horses, and selection for smaller size in laboratory mice has also increased life span, with opposite trend in larger individuals. Shorter mean lifespan can be explained by different mechanisms including earlier onset of senescence, higher mortality and increased rate of ageing. According to one hypothesis, faster ageing is the main reason for the relative short life span in large dogs, thus these breeds are characterised by an abnormally shortened old and senior period. Most researchers believe that selection for greater size in dogs at the later stage of domestication (using smaller breeds as the starting population) involved heavily the insulin-like growth factor-1 pathway, which apart from allowing for rapid early growth, had many side-effects which led to truncated life span.The role of inbreeding among breeds is also not negligible, as among dogs of the same body size, mongrels live longer.
Apart from size, behavioural/personality traits may also affect life span of dogs. Dog breeds with a more trainable character tend to have a longer life span. It can be argued, however, that not trainability itself, but the docility achieved by reduced stress to anthropogenic factors plays the key role.
In sum, it seems that life span of the dogs in general, and dog breeds in particular might have been affected by various (often opposing) selective factors either in parallel (e.g. decreasing size and increasing docility during early domestication) and sequentially in the course of domestication (e.g. new selection for large body size). It is possible that phenotypically similar ageing processes may actually be controlled or driven by different biological mechanisms. We aim at determining different parameters of ageing in dogs (e.g. start of ageing), comparing these values across breeds, and identifying genetic, biochemical and physiological pathways behind the different selective factors.
How old dogs should be considered as old?
Various authors use different threshold for ageing independently of the cohort they investigate. In the beagle for which median age is estimated at 13.3 years, Studzinski et al. (2006) introduced five periods: young adult (1-3 years), adult (3-6), middle aged (6-8), old (8-10), senior (11+) individuals. The beagle life span seems to correspond well to 11-12 years of age which was calculated for all pet dogs by, however only 36% of dog breeds listed in O’Neill et al (2013) reach this median age. To solve this problem in this project we will use mean/median life span for each breed as a reference, and divide the actual age of the dog by this value. In this case 0.5 means that the dog’s current age is half of the expected lifespan for its breed, while a relative age of 1.1 means that the dog current age is 10% beyond that expected on average for the breed. Using the relative age of individuals allows putting various breeds and cross-breeds in the same data set when one investigates life-long changes of different phenotypic parameters. Note that this method assumes a linear relationship between all life periods in dog breeds that may not be the case. For a more accurate calculation one would need the estimation of breed specific age period spans. We aimed to develop this scale at the end of the ERC period.