Synergistic and heterogeneous aging using composite phenotypes and multiple organ systems aging clocks

Assessing aging pace through biological age offers a precise perspective and underscores the need for further investigation into organ-level disparities. This observational study utilized multi-scale phenotypes from the Taizhou Imaging Study, encompassing brain imaging, cognitive assessment, blood biochemistry, omics, and physical measures. A total of 904 individuals (403 men and 501 women) aged 55-65 years were included. Age correlations with single and composite phenotypes were assessed, and multi-modal aging clocks were developed, incorporating organ systems, cognition, and the whole body. Here we show that composite phenotypes, such as those of cardiovascular system and bone, alter with age progression and could serve as aging clock features. Despite existing connections among various organs’ aging rates, their low intensity (under 0.25) indicates the variability of aging. Accelerated aging in the brain (mediating 12.46%, 95% CI: 4.37% to 24.44%) and kidneys (mediating 6.94%, 95% CI: 1.08% to 18.63%) partially mediates the relationship between smoking and the decline in olfactory identification. The diversity of organ aging is also evident as accelerated aging extends from the cardiovascular system to the kidneys and brain with increasing metabolic risk factors. Moreover, the biological ages of cardiovascular system, bone, metabolism, brain and the whole body show stronger associations with cardiovascular events risk than chronological age. The overlap between composite phenotypes and biological age provides valuable insights into multi-phenotypic aging. The unearthing of the heterogeneity in aging processes could further inform the development of personalized interventions to slow organ-specific aging and better manage age-related health problems. Aging affects different parts of the body in different ways, but most studies focus on single organs or single health measures. This study aimed to understand how aging unfolds across multiple organs and systems, and how these patterns relate to lifestyle factors and future disease risk. Using health and imaging data from middle-aged adults in rural China, we built “aging clocks” that track changes in traits across organs such as the heart, brain, bones, and metabolism. We found that some organs age faster than expected for a person’s age, and this uneven aging was linked to lifestyle risks like smoking and to future heart disease. These findings highlight the importance of targeting organ-specific aging to improve health in later life. Li et al. analyze multi-scale phenotypes to investigate heterogeneity in multi-organ aging patterns. They find that accelerated aging in organs such as the cardiovascular system, brain, kidneys, bone, and metabolism is associated with organ-specific links to lifestyle factors, health status, and cardiovascular risk.