Prevention and improvement of sarcopenia with 5-ALA

Professor

NAKAJIMA Osamu

Sarcopenia, the phenomenon of muscle strength and mass decreasing with aging, reduces the quality of life, and it is desirable both personally and socially to slow its progression. Muscle function and mitochondrial activity are closely related, and the decline in mitochondrial (Mt) activity due to aging is thought to be one of the causes of sarcopenia. In mice with a genetic knockout of 5-ALA synthase 1 (ALAS1), an essential enzyme for the biosynthesis of the mitochondrial cofactor heme, sarcopenia is accelerated (Figure 1), and in these muscles, mitochondrial abnormalities (Figure 2) and decreased autophagy (Figure 3) are observed. We found that abnormal mitochondria produced due to aging are typically removed by autophagy, and when autophagy is impaired, abnormal mitochondria accumulate, potentially accelerating sarcopenia. Furthermore, administering 5-ALA, the product of ALAS1, to ALAS1 knockout mice improves sarcopenia and autophagy decline (Figures 1-3). Based on these findings, we hypothesize that by taking 5-ALA, a supplement already used in other contexts, it may activate autophagy and help prevent or improve sarcopenia in humans. We are continuing our research in this area.

▲Figure 1: Decrease in muscle mass (A), muscle strength (B), and exercise endurance (forced running distance) in ALAS1 knockout mice (A1+/-), and recovery of these parameters with 5-ALA administration (C).

▲Figure 2: Atrophied mitochondria in the skeletal muscles of ALAS1 knockout mice (B) and recovery of mitochondrial abnormalities with 5-ALA administration (D) (A: wild-type mice, C: 5-ALA administered wild-type mice).

▲Figure 3: Decreased protein expression of total LC3 and LC3-II in the skeletal muscles of ALAS1 knockout mice (A1+/-) (LC3 protein expression serves as an indicator of autophagy activity) and recovery of these expressions with 5-ALA administration.