Short mitochondrial protein may help protect the aging heart from inflammation and failure
Researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have discovered that a relatively short protein may play an important role in protecting the aging heart. The protein, known as STMP1, is made up of 47 amino acids and helps maintain the internal structure of mitochondria, which are parts of cells that produce energy. The preclinical findings…
Researchers from the Yong Loo Lin School of Medicine at National University of Singapore have discovered that a short protein called STMP1 may help protect aging hearts from inflammation and failure. STMP1 is composed of 47 amino acids and plays a role in maintaining the structural integrity of mitochondria, which are energy-producing components within cells.
The study, published in Circulation, suggests that STMP1 levels decline in heart tissue associated with aging and a condition called inflammaging, which involves chronic low-grade inflammation in older individuals.
The researchers found that when STMP1 was deficient, it led to damaged mitochondria, persistent inflammation, and weakened heart function. This occurred because the loss of STMP1 caused cristae – folded inner membranes within mitochondria – to be damaged, resulting in mitochondrial DNA leaking into the cell. The cell then mistook the leaked DNA for an infection, triggering an immune response known as the cGAS–STING pathway.
This inflammatory response further disrupted energy production and led to the death of heart muscle cells.
The study demonstrated that restoring STMP1 using a gene delivery system or blocking the inflammation pathway with a drug could protect heart function in preclinical models. However, administering the inflammation-blocking treatment after significant mitochondrial damage had already occurred did not restore heart function. Professor Roger Foo, the corresponding author of the study, suggests that targeting STMP1 or the inflammation pathway it regulates could potentially help treat the underlying cause of heart failure rather than just its symptoms.
The findings imply that STMP1 could serve as a possible treatment target or biomarker for identifying aging or failing hearts. Nonetheless, the research is still at the preclinical stage, and further studies are required to evaluate the effectiveness of these approaches in patients. The researchers plan to continue their investigations using larger and more disease-relevant models to better understand how STMP1 supports mitochondrial structure and whether its levels could serve as an early indicator of heart failure risk.
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