# Spontaneous aging-associated inflammation and genome instability in the immune system of turquoise killifish

## TL;DR

Turquoise killifish show rapid immune system aging with inflammation and DNA damage, offering a model for studying and targeting aging interventions.

## Contribution

The study reveals age-related immune system changes in turquoise killifish, including inflammation and genome instability.

## Key findings

- Old killifish show increased inflammation markers in their immune system.
- Immune progenitors from old killifish display elevated DNA damage markers.
- Killifish exhibit immune system aging within less than 10 weeks.

## Abstract

Turquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates that recapitulate key aspects of human aging. However, the molecular and cellular causes of systemic aging in killifish are poorly understood. Here we ask whether killifish undergo age-dependent changes in the main hematopoietic organ (kidney marrow), which may contribute to systemic aging. To characterize immune aging in killifish, we used single-cell RNA sequencing, cytometry and functional in vitro assays on kidney marrow cells from young-adult and old killifish, together with proteomic profiling of both kidney marrow-derived cells and plasma. We show that old killifish display increased markers of inflammation; while immune progenitor-like cell clusters from adult killifish display markers of active proliferation and replication-independent DNA repair, immune cell progenitors from old killifish display increased markers of DNA damage. Within less than 10 weeks, killifish exhibit age-related transformations within the immune system, underscoring the value of killifish for developing immune-system-targeted antiaging interventions.

Turquoise killifish are naturally short-lived vertebrates that serve as a model system for aging. The authors show that killifish exhibit age-related transformation in the immune system, which rapidly develops inflammation, genome instability and functional decline.