Clinical Connections  –  Spring 2022

Balázs Szladovits, Associate Professor of Clinical Pathology

Ageing research has come a long way since the late middle age’s holy grail of procurement of the philosopher’s stone through to the 15th century quest to find the fountain of youth, to our current scientific understanding. Recent advancements of biotechnology and big data-aided research is causing an explosion in this intriguing field. An exciting new tool in the arena is the discovery of the ‘epigenetic clock’ – pioneered by Professor Steve Horvath at UCLA.   

Epigenetics is the study of processes that can change gene expression, without changing the DNA sequence itself. One such change is DNA methylation, which can activate or turn off individual genes. With ageing, DNA methylation appears to change in a predictable manner. The speed of this is slightly different for everyone, based on genetics and likely lifestyle. This new tool based on analysis of the epigenetic data of an individual can reveal their ‘biological age’. While everyone’s chronological age advances at the same speed, individual’s ‘biological clocks’ have different paces.

The application of this clock on large human epidemiological data sets revealed that discordance between the predicted (epigenetic age) and chronological age is associated with diverse age-related pathologies, when the former is greater than the latter. Since then, an ever-increasing scope of pathologies have been found to be associated with accelerated epigenetic ageing. These features are consistent with the view that the epigenetic clock in effect measures biological age – which is an indicator of health; a notion that is supported by the clock’s ability to predict time-to-pathology and all-cause (non-accidental) mortality.

Biological age can be contrasted with chronological age as a result of epigenetics research

Finding reliable biological measures of ageing (and general health) has been a longstanding research aspiration, based on the premise that such biomarkers would lead to the understanding of how ageing increases susceptibility to certain diseases, along with the identification of strategies for promoting healthy ageing.

Sadly, the Covid pandemic has highlighted the serious consequences of ill health, especially among the elderly. While lifespan extension still appears elusive, increasing the ‘healthspan’ (years in good health) could have major implications for ageing Western societies and their overburdened health systems.

The numerous studies employing this new research tool have revealed that many of our previously thought healthy habits indeed are associated with slower epidemiologic ageing, including avoidance of obesity, smoking, and following a healthy diet (high vegetable and fish intake) and exercising.

Another exciting area of ageing research is the search of anti-ageing interventions, which were mostly limited previously to animal models, due to the length of time it would take to study it in humans.

An exciting recent collaboration between RVC scientist Dr Balázs Szladovits, Dr Ken Raj from Public Health England and Professor Steve Horvath of UCLA has resulted in the development of an epigenetic clock for cats, and even a dual clock for cats and humans based on the same mathematical algorithm that assesses the age as a percent of the known maximal lifespan, therefore bridging the large age difference between ourselves and our companions with remarkably high correlation. Furthermore, this collaboration has also valuably contributed to the work of the Mammalian Methylation Consortium, which has developed a pan-mammalian epigenetic clock, based on 348 species. 

The fact that such a clock could be developed highlights a highly conserved programing of the ageing process across all these species, which is paving the way for new discoveries of the molecular details of this process. If an anti-ageing intervention is successful to slow the biologic clock in one mammalian species, it is likely to work in humans and other mammals, opening novel possibilities within this field.

This exciting collaboration was made possible by all the clinical samples that are submitted to the RVC’s Diagnostic Laboratories, from which residual samples are stored in our valuable DNA bank, under strict ethical regulations.

With this novel epigenetic clock for cats, the transatlantic research group’s goal is to apply this tool in studying the ageing and disease processes of cats, both for their own benefit, but also as a model for humans, given the similar environment our companions live in (compared to laboratory animals in artificial environments).

Lastly, but not least, given the precision of the new epigenetic clock, it could even be an invaluable tool for age determination in the forensic field, with much higher accuracy than was previously possible.

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