Deciphering the Factors of Longevity Through a Multi-Omics Study in Long-Lived Individuals in Hong Kong

Aging

Aging, Multi-omics, AI-based tool, Longevity

Population aging is changing societal dynamics and poses significant global challenges. By 2050, an estimated 1.6 billion people worldwide will be over age 65. Because aging is the primary risk factor for many common chronic diseases, it is essential to reduce the burden of age-related illnesses and promote healthy aging. Hong Kong has one of the largest proportions of elderly adults and has the highest life expectancy in the world, with approximately 11,575 centenarians reported in 2021. Thus, the long-lived population in Hong Kong is a valuable resource for studying healthy aging. Longevity is a complex trait influenced by genetic, environmental, and behavioral factors. To unveil the mechanisms leading to longevity and healthy aging, researchers focused on centenarians who are extremely long living. Comparisons between long-lived individuals (LLIs) and others have identified several genetic factors and protein markers associated with longevity. Previous centenarian studies revealed that centenarians and their offsprings have a 5-fold lower risk of developing age-related diseases such as Alzheimer's disease and higher cognitive reserve. Certain protein signatures predict longer survival and centenarians acquire aging signatures much later than elderly in the general population. Certain healthy lifestyle leads to higher chance becoming centenarians, including never smoking, exercise and greater dietary diversity. Despite emerging studies on centenarian population, an integrated approach to understand diverse molecular signatures of longevity is still lacking. Moreover, most of the centenarian studies are based on European descents. To conclude, a multi-omics study examining the genetic, proteomic, metabolomic, and microbiota profiles of LLIs in Chinese population is necessary. Hence, the study proposed herein aims to identify multi-omics biomarkers that can be used to monitor aging processes and related diseases. In addition, it will provide candidate modifiable factors to promote healthy aging, focusing on Chinese population and local Hong Kong population for the first time. Ultimately, the insights gained from this research will inform the development of effective strategies to enhance healthy aging and improve the quality of life of our local aging population.

The proposed research is a cross-sectional study that will last for 5 years. 500 individuals aged 95 years or older (i.e., LLIs) from various communities in Hong Kong will be recruited. LLIs will be recruited through advertisements as well as collaboration with geriatric community centers and non-government organizations (NGOs). Participants will be recruited at geriatric centers and NGOs to collect demographic information, family history, medical history, and medication records. Blood samples for clinical chemistry and multi-omics study will be collected. Furthermore, cognitive and functional assessment using various scoring systems will be performed to assess cognition and activities of daily living. In addition, a control cohort of elderly people (aged 65-94 years, n = 2,000) based on our in-house Alzheimer's disease registry and community cohort will be developed. Accordingly, demographics, clinical profiles, cognitive and functional scores, and multi-omics data between the LLI and control cohorts will be compared.

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China