Chronological age reflects the passage of time, but it does not fully explain why people of the same age often show large differences in health, immune function, and disease risk. Biological age instead captures the functional state of cells, tissues, and organs, providing a more informative measure of aging-related decline. Advances in aging biology have identified a set of conserved molecular and cellular processes—often referred to as the hallmarks of aging—including epigenetic alterations, mitochondrial dysfunction, cellular senescence, and dysregulated intercellular communication, which collectively drive age-related functional deterioration. Because aging is a major driver of chronic diseases, understanding biological aging is essential for linking molecular changes to clinical outcomes and healthspan.

In this research direction, biological aging is studied as a systemic process spanning organ-specific, immune, and epigenetic dimensions, giving rise to substantial heterogeneity among individuals. Such heterogeneity is reflected in age acceleration and distinct aging endotypes, which in turn shape clinically meaningful outcomes, including immune remodeling, age-associated comorbidities, and mortality risk. Understanding these outcomes requires linking observable aging phenotypes to their underlying biological programs, from coordinated transcriptomic and proteomic changes to the dysregulation of transposable elements. Viewed through this lens, aging trajectories are not fixed but can be reshaped by therapeutic interventions, highlighting the plasticity of human aging across populations and contexts. This project is in collaboration with Professor Linos Vandekerckhove at Ghent University and Professor Cheng-Jian Xu , Professor Yang Li at CiiM.

Systemic, organ-specific, and epigenetic aging metrics capture heterogeneous aging patterns in a treated HIV population.

Historically, it has been understood that the immune response that targets a specific pathogen was governed by the adaptive immune system, while innate immune cells, including macrophages, were merely considered as the initial natural barrier of the immune system. However, recent studies have unveiled that, akin to adaptive immune cells such as T cells and B cells, innate immune cells are also capable of developing short-term or long-term immune memory. Several clinical trials have illustrated that this non-specific memory can also enhance the immune response against the second infection of the pathogen, even other unrelated pathogen, including COVID-19. In Netea et al. 2016 reviewed this phenomenon as the concept of trained immunity. Accumulating evidence suggests that epigenetic reprogramming is a core driving element of trained immunity. Deciphering the mechanisms behind trained immunity and how to successfully harness it for vaccine development will be pivotal questions in this research field. This project is in collaboration with Senior Researcher Yutaro Kumagai at AIST and Professor Jun Kunisawa and his student Kei Ishida at Osaka University.

Epigenetic regulation on chromatin during macrophage hysteresis (memory) generation.