Pentadbiran NMN memperbaiki kegagalan jantung akibat disfungsi mitokondria

Myocardial mitochondria are primary sites of myocardial energy metabolism. Mitochondrial disorders are associated with various cardiac diseases. Mitochondrial translation defects cause not only mitochondrial dysfunction but also decreased nicotinamide adenine dinucleotide (NAD+ ) levels, leading to impaired lysosomal acidification and autophagy. In this study, reseachers investigated whether nicotinamide mononucleotide (NMN) administration, which compensates for decreased NAD+ levels, improves heart failure because of mitochondrial dysfunction. NMN administration reduced damaged lysosomes and improved autophagy, thereby reducing heart failure and extending the lifespan in p32cKO mice. The study found that lysosomal damage due to mitochondrial dysfunction induced ferroptosis, involving the accumulation of iron in lysosomes and lipid peroxide.

1. Pemberian NMN meningkatkan fungsi lisosom dan mengurangkan kegagalan jantung pada tikus dengan disfungsi mitokondria

The study found that NMN administration improved lysosomal function and reduced heart failure in mice with mitochondrial dysfunction. Specifically, NMN supplementation reduced damaged lysosomes and improved autophagy, leading to a reduction in heart failure and an extension of lifespan in these mice. These findings suggest that NMN supplementation strongly affects lysosomal function, offering a potential therapeutic approach for heart failure.(as shown in Rajah 1)

Rajah 1 

2. Pemberian NMN mengurangkan feroptosis di jantung

Pemberian NMN mengurangkan feroptosis di jantung, iaitu satu bentuk kematian sel yang disebabkan oleh pengumpulan peroksidasi zat besi dan lipid. Pengurangan ferroptosis ini dikaitkan dengan peningkatan ekspresi glutathione peroxidase 4 (GPX4), yang merupakan enzim utama yang terlibat dalam pencegahan peroksidasi lipid. Penemuan ini mencadangkan bahawa pemberian NMN mungkin melindungi daripada kegagalan jantung dengan mengurangkan feroptosis di jantung.

Rajah 2

3. Pentadbiran NMN memulihkan ekspresi gen di jantung

Kajian mendapati pentadbiran NMN memulihkan ekspresi beberapa gen di jantung yang telah dikurangkan pada tikus dengan disfungsi mitokondria. Gen-gen ini terlibat dalam pelbagai proses selular, termasuk fungsi mitokondria, tekanan oksidatif, dan keradangan. Penemuan ini mencadangkan bahawa pentadbiran NMN mungkin memperbaiki fungsi jantung dengan memulihkan ekspresi gen dalam jantung.

Rajah 3

4. Pentadbiran NMN meningkatkan fungsi mitokondria di jantung

Kajian mendapati bahawa pentadbiran NMN memperbaiki fungsi mitokondria di jantung, seperti yang dibuktikan oleh peningkatan bilangan salinan DNA mitokondria dan ekspresi gen yang terlibat dalam biogenesis mitokondria. Penemuan ini mencadangkan bahawa pentadbiran NMN mungkin melindungi daripada kegagalan jantung dengan memperbaiki fungsi mitokondria di jantung.

Rajah 4

Mitochondria are the main organelles for energy production, and mitochondrial dysfunction causes serious diseases associated with aging. We previously found that (1) the expression of NAD+ synthase expression was decreased owing to mitochondrial dysfunction and lysosomal and autophagic function was impaired owing to decreased NAD+ biosynthesis (Yagi et al, 2021) as an additional cause of the exacerbation of chronic heart failure associated with aging. This study shows that NMN administration improves lysosomal function and cell death by ferroptosis when NAD+ levels are improved. In the near future, we aimed to apply NMN to clinical use in aging- and lysosome-related diseases.

Penafian