Differential Organ Ageing Is Associated With Age-Related Macular Degeneration

Area of Science:

• Ophthalmology
• Gerontology
• Genetics

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss, with age, genetics, and smoking as key risk factors.
• Biological age, a measure of cellular and tissue aging, can differ from chronological age, impacting health outcomes.
• Understanding the relationship between organ-specific biological aging and AMD development is crucial for risk prediction and prevention.

Purpose of the Study:

• To predict biological age across multiple organ systems using machine learning.
• To investigate the association between organ-specific biological age and incident age-related macular degeneration (AMD).
• To explore the relationship between AMD genetic risk scores and differential organ system aging.

Main Methods:

• Utilized machine learning to calculate biological age for immune, cardiovascular, pulmonary, renal, musculoskeletal, metabolic, and hepatic systems.
• Analyzed physiological and physical markers from the UK Biobank cohort.
• Correlated organ system biological ages with incident AMD data from electronic health records and AMD genetic risk scores.

Main Results:

• Most organ systems exhibited accelerated aging in individuals who developed AMD post-recruitment compared to controls.
• The immune system showed the most significant accelerated aging, particularly in younger males.
• AMD patients displayed slower hepatic system aging, notably in females, and overall AMD genetic risk correlated with faster aging across most organs.

Conclusions:

• Differential organ system aging is associated with age-related macular degeneration (AMD).
• Immune system aging is strongly linked to AMD development, especially in younger males.
• AMD genetic risk variants influence the aging trajectory of various organ systems, highlighting a complex interplay between genetics and aging in AMD pathogenesis.