Molecular Regulation of Aging

Members

Keywords

healthy longevity, aging regulation, nutrition, diet, macronutrient, protein, metabolic health, frailty, dementia, vitamin C, ascorbic acid, senescence marker protein-30 (SMP30), gluconolactonase, antioxidant, epigenetics, DNA demethylation.

Major Research Titles

1. Nutrition and aging
2. Aging and vitamin C

Profile

The molecular regulation of aging aims to achieve healthy longevity by unraveling the relationship between nutrition and aging.
A well-balanced diet has long been recommended as a secret to longevity. However, what exactly is a well-balanced diet? Lately, much attention has been paid to the relationship between the caloric ratio of macronutrients (protein, carbohydrates, and fats) and health, aging, and longevity. Recently, we have found that the optimal dietary protein ratio for maintaining metabolic health in mice toward old age is 25%-35%. We are now exploring whether getting the right balance of macronutrients can help prevent problems such as frailty, muscle loss, and dementia, and increase the number of healthy years.
We also focus on the relationship between aging and vitamin C. We have independently generated vitamin C synthesis-deficient mice (SMP30-knockout mice), which cannot synthesize vitamin C like humans, and revealed that long-term vitamin C deficiency shortened the lifespan. Vitamin C is deeply involved in the regulation of gene expression through epigenetics as a cofactor for DNA demethyltransferases. The shortened lifespan caused by vitamin C deficiency may be attributed to epigenetic abnormalities.

References

1. Kondo Y, Sato A, Osakabe N, Minowa T, Hung YL, Machida S, Ishigami A. Vitamin C is essential for proper myogenic differentiation. Arch Biochem Biophys 776, 110704, 2026
2. Sato A, Kondo Y, Ishigami A. The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging. J Physiol Sci, 74(1), 29, 2024
3. Kondo Y, Aoki H, Masuda M, Nishi H, Noda Y, Hakuno F, Takahashi SI, Chiba T, Ishigami A. Moderate protein intake percentage in mice for maintaining metabolic health during approach to old age. GeroScience 45(4), 2707-2726, 2023
4. Kondo Y, Ishigami A. Involvement of senescence marker protein-30 in glucose metabolism disorder and nonalchoholic fatty liver disease. Geriatr Gerontol Int 16 (Suppl. 1), 4-16, 2016
5. Kondo Y, Hasegawa G, Okada H, Senmaru T, Fukui M, Nakamura N, Sawada M, Kitawaki J, Okanoue T, Kishimoto Y, Amano A, Maruyama N, Obayashi H, Ishigami A. Lepr^db/db mice with senescence marker protein-30 knockout (Lepr^db/dbSmp30^Y/-) exhibit increases in small dense-LDL and severe fatty liver despite being fed a standard diet. PLoS ONE 8(6), e65698, 2013
6. Kondo Y, Sasaki T, Sato Y, Amano A, Iwama M, Handa S, Shimada N, Fukuda M, Akita M, Lee J, Jeong KS, Maruyama N, Ishigami A. Vitamin C depletion increases superoxide generation in brains of SMP30/GNL knockout mice. Biochem Biophys Res Commun 377, 291-296, 2008
7. Kondo Y, Inai Y, Sato Y, Handa S, Kubo S, Shimokado K, Goto S, Nishikimi M, Maruyama N., Ishigami A. Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc Nat Acad Sci USA 103, 5723-5728, 2006
8. Ishigami A, Kondo Y, Nanba R, Ohsawa T, Handa S, Kubo S, Akita M, Maruyama N. SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span. Biochem Biophys Res Commun 315, 575-580, 2004