Organ Communication via Systemic Signals

Liver-heartThe tissue-specific roles of known longevity pathways in the regulation of lifespan have been reported from several studies. However, it is unclear how genetic manipulation of these pathways within certain tissue can result in a systemic effect on organism’s fitness and survival. Besides cell-autonomous mechanisms (e.g., autophagy), it has become much appreciated that inter-tissue communication is also attributed to age-dependent decline of cardiac function. However, such non-autonomous regulation of cardiac aging has not yet been identified. The liver (oenocytes in flies) is a major endocrine organ, and aging significantly alters liver morphology and function. Patients with liver dysfunction, such as cirrhosis, often show increased cardiac arrhythmias. Thus, there is a clear connection between liver and heart.

Through a genetic screen, we identified oenocyte-derived upd3, an interleukin 6 (IL-6)-like pro-inflammatory cytokine in Drosophila, is a key hormonal factor mediating oenocyte-heart communication and cardiac aging.. Furthermore, we show that age-dependent impairment of peroxisome import is a major cause of oenocyte dysfunction, upd3 induction, and systemic inflammation. Thus, our findings establish peroxisome as a novel regulator of tissue aging and chronic inflammation (inflammaging). Our studies also reveal a new paradigm for cardiac aging, which is that age-related cardiac diseases are rooted.