The faster your epigenetic clock ticks, the higher the chance your health is in decline

Imagine a hidden clock that ticks inside your body at its own pace, influencing not just your appearance as you age, but the age of your cells and tissues, too.

This hidden internal clock, known as biological age, can be different from your chronological age – the number of years you’ve been alive. When biological age is greater than chronological age, we call it “biological age acceleration”.

Epigenetic age, one of the most promising biomarkers of ageing, is estimated biological age based on DNA methylation levels at the specific genes across the genome. DNAm is an epigenetic mechanism that occurs by the addition of a methyl group to CG dinucleotide in DNA, because of ageing, lifestyle choices, and environmental factors.

It can reflect how old your body is at the molecular level, potentially capturing the risk of age-related diseases and longevity beyond chronological age.

Read more: Ultra-processed foods are making us old beyond our years

During recent years, a number of algorithms have been developed to estimate epigenetic age: HorvathAge, HannumAge, PhenoAge, GrimAge, GrimAge2, FitAge, and DunedinPACE.

Monash researchers found ground-breaking evidence from 11-year longitudinal studies that epigenetic age acceleration affects both physical strength and cognitive sharpness, potentially explaining why some people age faster and are in poorer health than others.

Lead author Dr Aung Zaw Zaw Phyo, a research fellow at the School of Public Health and Preventive Medicine said:

“In our latest studies involving 560 Australians aged older than 70, females compared to their male counterparts showed lower epigenetic ageing and better cognitive performance, but had higher frailty scores marked by physical weakness. This finding reflects the male-female health paradox, in that females live longer than males, but are more likely to experience disease burdens.”

Faster epigenetic ageing, particularly as measured by the latest indices – GrimAge, GrimAge2, FitAge and DunedinPACE – are linked to a higher burden of frailty over time, with more females than males experiencing a greater burden.

The impact of a rapidly ticking epigenetic clock extends beyond just physical health, and appears to significantly impair cognitive function in later life.

The research also revealed that females with accelerated epigenetic ageing, particularly accelerated GrimAge and GrimAge2, experienced a more pronounced cognitive decline in information recall and memory over time.

Accelerated epigenetic ageing results in a different challenge for males – a significant slowing in mental processing speeds, which is an important component of decision-making and problem-solving. Even more alarming, males with faster epigenetic ageing were found to have nearly double the risk of developing dementia in an average of seven years.

These novel findings, recently published in the journals GeroScience, Age and Ageing, and Alzheimer’s and Dementia: Diagnostic Assessments and Disease Monitoring, provide new insights into the ageing process.

Senior author Professor Joanne Ryan, from Monash’s School of Public Health and Preventive Medicine, said:

“Findings from our series of studies suggest that epigenetic age acceleration can be considered a useful marker of physical and cognitive deterioration in later life, beyond chronological age. Understanding the link between this hidden biological clock and physical and cognitive functioning opens the door to explore new approaches and interventions for improving health outcomes and managing age-related conditions.”

“The evidence we found for sex-specific associations suggests that males and females perhaps experience the ageing process in fundamentally different ways, and underscores the importance of developing sex-specific interventions and healthcare strategies in addressing age-related health disparities,” said Dr Phyo.