Aging Activates the Immune System and Alters the Regenerative Capacity in the Zebrafish Heart.

Hanna Reuter,Christoph Englert,Birgit Perner,Luise Rohde,Florian Wahl,Philipp Koch,Marco Groth,Katrin Buder

doi:10.3390/cells11030345

Hanna Reuter, Christoph Englert + Show 6 more

Open Access

https://doi.org/10.3390/cells11030345

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Abstract

Age-associated organ failure and degenerative diseases have a major impact on human health. Cardiovascular dysfunction has an increasing prevalence with age and is one of the leading causes of death. In contrast to humans, zebrafish have extraordinary regeneration capacities of complex organs including the heart. In addition, zebrafish has recently become a model organism in research on aging. Here, we have compared the ventricular transcriptome as well as the regenerative capacity after cryoinjury of old and young zebrafish hearts. We identified the immune system as activated in old ventricles and found muscle organization to deteriorate upon aging. Our data show an accumulation of immune cells, mostly macrophages, in the old zebrafish ventricle. Those immune cells not only increased in numbers but also showed morphological and behavioral changes with age. Our data further suggest that the regenerative response to cardiac injury is generally impaired and much more variable in old fish. Collagen in the wound area was already significantly enriched in old fish at 7 days post injury. Taken together, these data indicate an ‘inflammaging’-like process in the zebrafish heart and suggest a change in regenerative response in the old.

Highlights

Published: 20 January 2022The gradual decline of tissue functionality is the main reason humans suffer from age-related diseases
We identified the immune system as activated in the old fish and found muscle organization to deteriorate upon aging
In the context of the senescence-associated secretory phenotype (SASP), considered a hallmark of aging, high levels of inflammatory cytokines and immune modulators are secreted by senescent cells

Summary

Introduction

The gradual decline of tissue functionality is the main reason humans suffer from age-related diseases. The ability to replace missing or damaged tissue, organs or even entire body parts and functionally integrate these regenerates into the existing structures is limited to a few organs, including the liver, intestine, skeletal muscle and the hematopoietic system. Organ failure and degenerative diseases have a major impact on human health, especially when we age. Cardiovascular diseases are the leading cause of death, representing 32% of all deaths globally in 2019 (World Health Organization—www.who.int (accessed on 3 September 2021)). A considerable part of this morbidity and mortality is due to irreversible damage of the heart muscle. Myocardial infarction, the acute blockage of a coronary artery, leads to the formation of a non-contractile scar post injury that impairs heart function

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