Molecular Regulation of Aging

Theme Leader :
Akihito Ishigami, Ph.D.
Researcher :
Ayami Sato, Ph. D., Yuta Doshida, Ph. D.
Adjunct Researcher :
Yuka Takino, M.S.

aging, aging regulation, aging biomarker, antioxidant, ascorbic acid, senescence marker protein-30 (SMP30), gluconolactonase, vitamin C, reactive oxygen species, life span, Peptidylarginine deiminase (PAD), citrullinated protein, Alzheimer's disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD)

1. 1.Functional elucidation of Senescence Marker Protein 30 (SMP30)
2. 2.Vitamin C and aging
3. 3.Identification of senescence-associated genes and senescent cells using single cell transcriptome analysis
4. 4.Nutrition and aging
5. 5.Citrullinated protein and geriatric disease

Humans gradually deteriorate physiologically with aging as multiple biological events foster changes in the expression of critical molecules and thereby promote organic breakdown. The aim of our research group is early detection of these destructive factors by developing methodologies to analyze the relevant genes and proteins, then precisely controlling their activities.
We have discovered that the biomolecule SMP30, which acts to strengthen cellular resistance to both internal and external bodily injury, decreases in quantity and function with aging. Therefore, SMP30 is expected to become extremely useful as a biomarker of aging. Similarly, citrullinated protein has an important physiological purpose by forming the cornified layer of skin that covers the human body. Despite this beneficial function, citrullinated protein also has a negative side, because our recent research has shown that this protein's accumulation in the brain is a possible cause of Alzheimer's disease.
The aging continuum is a thread to which many biomolecules are bound; both environmental and hereditary factors contribute such molecules to mutually complex interactions. Our research is devoted to untying that thread precisely and usefully in the expectation of contributing to humanity the capacity for satisfying and healthful longevity.

1. 1.Yamaguchi T, Yamamoto Y, Egashira K, Sato A, Kondo Y, Saiki S, Kimura M, Chikazawa T, Yamamoto Y, Ishigami A, Murakami S. Oxidative Stress Inhibits Endotoxin Tolerance and May Affect Periodontitis. J Dent Res. 2023 Mar;102(3):331-339.
2. 2.Takisawa S, Takino Y, Lee J, Machida S, Ishigami A. Vitamin C Is Essential for the Maintenance of Skeletal Muscle Functions. Biology (Basel). 2022 Jun 23;11(7):955.
3. 3.Hung YL, Sato A, Takino Y, Ishigami A, Machida S. Influence of oestrogen on satellite cells and myonuclear domain size in skeletal muscles following resistance exercise. J Cachexia Sarcopenia Muscle. 2022 Oct;13(5):2525-2536.
4. 4.Palko SI, Saba NJ, Mullane E, Nicholas BD, Nagasaka Y, Ambati J, Gelfand BD, Ishigami A, Bargagna-Mohan P, Mohan R. Compartmentalized citrullination in Muller glial endfeet during retinal degeneration. Proc Natl Acad Sci U S A. 2022 Mar 1;119(9):e2121875119.
5. 5.Takigawa M, Tanaka H, Obara T, Maeda Y, Sato M, Shimazaki Y, Mori Y, Ishigami A, Ishii T. Utility of the Berlin Initiative Study-1 equation for the prediction of serum vancomycin concentration in elderly patients aged 75 years and older. Pharmazie. 2022 Feb 1;77(2):76-80.
6. 6.Sato A, Takino Y, Yano T, Fukui K, Ishigami A. Determination of tissue-specific interaction between vitamin C and vitamin E in vivo using senescence marker protein-30 knockout mice as a vitamin C synthesis deficiency model. Br J Nutr. 2022 Sep 28;128(6):993-1003.