New research from the University of Adelaide has explored the genomic links within the index used to measure healthy ageing - Intrinsic capacity (IC), paving the way for potential targeted interventions.
Intrinsic capacity was introduced by the World Health Organization (WHO) in 2015 as a marker of healthy ageing and it represents an individual's physical and mental attributes across five key domains: cognition, vitality, sensory function, and psychological health.
This study analysed the genetic data of more than 57,000 participants through the UK Biobank (UKB) and the Canadian Longitudinal Study on Ageing (CLSA) to identify genetic variants linked to IC.
The study revealed that genetic factors account for about 20 to 25 per cent of the variability in IC, with the remaining influenced by environmental and lifestyle factors. A genome-wide association analysis discovered 38 independent genetic variants across 10 genomic loci linked to IC.
"Our study is the first of its kind to explore the genetic architecture of IC," says Associate Professor Azmeraw Amare, senior author and NHMRC Emerging Leadership Fellow at the University of Adelaide.
"These findings provide a foundational understanding of the biological mechanisms that support healthy ageing.
"By identifying the genetic factors that influence intrinsic capacity, we can begin to develop targeted interventions to help people maintain their functional abilities as they age."
The findings, published in the Journal of Gerontology: Biological Sciences, revealed strong correlations between IC and traits such as lung function, grip strength and cognitive performance.
"The identified genes are involved in critical biological processes relevant to healthy ageing process such as metabolism, immune function, neurodegeneration, and cellular ageing," says first author Melkamu Beyene, PhD candidate with Adelaide Medical School.
"These genes are highly expressed in the brain, heart, muscle, and body tissue."
Since its introduction, IC has been considered powerful predictor of many subsequent outcomes, including mortality, care dependence, and a range of chronic diseases, even after accounting for personal characteristics and multimorbidity.
"Unlike disease and disability, which are relatively late and separate measures of poor health in older adults, IC provides a holistic and continuous framing of health that mirrors recent work on the complex and dynamic biological changes that drive aging," says Mr Beyene.
Overall, these results enhance our understanding of the genetic underpinnings of IC and offer a foundation for exploring biological mechanisms that may serve as a baseline for future research, according to Professor Renuka Visvanathan, head of the Adelaide Geriatrics Training and Research with Aged Care Centre.
"This research opens the door to personalised approaches for promoting healthy ageing," says Professor Visvanathan, also senior author on the paper.
"These insights could help clinicians better predict and support healthy ageing trajectories."
Professor John Beard, Irene Diamond Professor, Director, International Longevity Center at Columbia University, who was also involved in the study said intrinsic capacity was developed to shift the focus of ageing policy from disease to function.
"This study provides the biological foundation needed to translate that vision into action," he said.
