老化：加齢性疾患や免疫低下のリスクを予測できる炎症性老化「時計」

A new aging clock can identify individuals with an increased risk of developing cardiovascular and other diseases, according to a paper published in Nature Aging. The tool, which uses blood-based signals that drive chronic inflammation throughout the body, may have implications for early diagnosis and intervention.

Although the interplay between the immune system and many age-related diseases is well-characterized, immune metrics that can be used to predict those most at risk are few and far between.

David Furman and colleagues studied blood samples from 1,001 individuals (aged 8–96 years; 66% female) as part of the 1000 Immunomes project. The goal of the project is to investigate how signatures of chronic, systemic inflammation change as we age. Artificial intelligence was then used to develop a new immune metric, or inflammatory ‘clock’ of aging, known as ‘iAge’. The clock is based on the concept that levels of specific immune cells and proteins in the blood fluctuate with age; however, for some, this occurs earlier, and is defined as their ‘iAge’. The authors found that people with an older iAge show these patterns of age-related systemic inflammation earlier and are more likely to develop multiple long-term health conditions including lowered immunity, cardiovascular disease, or become frail at a younger age. Age-related release of the chemokine CXCL9 — a protein that normally helps activate T cells in the immune system — was further identified as a key factor produced by the endothelium that speeds up the iAge clock. CXCL9 does so by promoting cellular senescence, the process by which cells are driven into a dysfunctional state, and impeding blood vessel function.

The authors conclude that the iAge clock offers a new method for identifying individuals at risk of developing age-related diseases and immunological decline, and suggests CXCL9 and other iAge proteins as potential new targets for their treatment.