Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine

Area of Science:

• Cellular and Molecular Biology
• Aging Research
• Cardiovascular Physiology

Background:

• Aging is linked to chronic inflammation, a risk factor for cardiovascular diseases.
• The non-autonomous regulation of age-related cardiac dysfunction by non-cardiac tissues is not well understood.

Purpose of the Study:

• To investigate the role of pro-inflammatory factors from non-cardiac tissues in cardiac aging.
• To identify the specific molecular mechanisms underlying age-related cardiac dysfunction.

Main Methods:

• Utilized Drosophila melanogaster as a model organism.
• Performed oenocyte-specific gene knockdown and overexpression.
• Analyzed upd3 expression levels and cardiac function (arrhythmia).
• Investigated peroxisomal import pathways and JNK signaling.

Main Results:

• Age-dependent induction of cytokine unpaired 3 (upd3) in oenocytes was identified as a key factor in cardiac aging.
• Oenocyte-specific upd3 knockdown prevented aging-induced cardiac arrhythmia.
• Impaired peroxisomal import and elevated JNK signaling in aged oenocytes triggered upd3 induction.
• Overexpression of Pex5 in oenocytes blocked upd3 induction and cardiac arrhythmicity.

Conclusions:

• Oenocyte-derived upd3 is a primary non-autonomous regulator of cardiac aging.
• Peroxisomal dysfunction in oenocytes contributes to cardiac aging via "peroxikines" like upd3.
• Targeting hepatocyte-specific peroxisomal import may offer therapeutic strategies for age-related cardiac dysfunction.