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Mutations accumulated in mitochondrial DNA associated with aging were earlier believed to cause aging by decreasing the energy-producing function (mitochondrial respiratory function). In this study, researchers at University of Tsukuba demonstrated that mitochondrial respiratory function is not reduced even when wild-type mice accumulated the same level of mutations as premature aging model mice, indicating the need to reinvestigate the conventional theory.

Tsukuba, Japan—The human genome is broadly classified into the genome residing in the cell nucleus (nuclear DNA) and the genome residing in the mitochondria (mitochondrial DNA: mtDNA). Mitochondria are cell organelles that produce energy essential for life activities through oxidative phosphorylation (mitochondrial respiration), and mtDNA encodes a set of genes required for mitochondrial respiration. Previous research has led to the widely accepted hypothesis that the accumulation of multiple mutations in mtDNA with aging induces a decline in mitochondrial respiratory function, resulting in the "mitochondrial theory of aging." Nevertheless, whether the decrease in mitochondrial respiratory function is actually due to these accumulated mutations has not been definitively established.

In this study, researchers demonstrated that mitochondrial respiratory function is not impaired even when wild-type mice accumulated mtDNA mutations to the same extent as in premature aging model mice.

These results suggest that the decline in mitochondrial respiratory function is not directly caused by mtDNA mutations alone. Furthermore, the results call for a reinvestigation of the "mitochondrial theory of aging." The research team will continue to explore how various mutations accumulated in mtDNA contribute to symptoms of premature aging, aiming to expand our understanding of the relationship between aging and mitochondrial dysfunction.

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This work was supported by the Grant-in-Aid for Scientific Research B [22H02536 and 23K23801 to K.N.] from the Japan Society for the Promotion of Science (JSPS), by the AMED-CREST [JP23gm1110006 to K.N.] from the Japan Agency for Medical Research and Development (AMED), by JST FOREST Program [JPMJFR204M to K.I.] and by JST SPRING [JPMJS2124 to H.T.] from Japan Science and Technology Agency (JST). This work was partly supported by the Grant-in-Aid for Scientific Research C [JP21441138 and JP24008885 to E. O.] from JSPS.

Original Paper

Title of original paper:

Mitochondrial Respiratory Dysfunction Is Not Correlated With Mitochondrial Genotype In Premature Aging Mice

Journal:

Aging Cell

DOI:

10.1111/ACEL.70085

Correspondence

Professor NAKADA Kazuto
Institute of Life and Environmental Sciences, University of Tsukuba

TAMASHIRO Hiroaki
Degree Programs in Life and Earth Sciences, Graduate School of Science and Technology, University of Tsukuba

Related Link

Institute of Life and Environmental Sciences

Degree Programs in Life and Earth Sciences, Graduate School of Science and Technology