Takehiko Kobayashi was born in Yokohama, Japan. In 1992, he obtained a Ph.D. from the Kyushu University under the supervision of Prof. T. Horiuchi. After working three years as a postdoc with Dr. Melvine DePamphilis at Roche Institute of Molecular Biology in New Jersey and National Institute of Health in Maryland, USA, he returned to Japan as an assistant professor and promoted to associate professor in National Institute for Basic Biology, Okazaki, Japan. In 2006, he became a full professor in National Institute of Genetics, Mishima, Japan. In 2015, he moved to Institute of Molecular and Cellular Biosciences, The University of Tokyo. His research interest is the relationship between genome stability, cellular senescence and rejuvenation. He has received awards, “Prize for Science and Technology” by the Ministry of Education, Culture, Sports, Science and Technology, Japan” in 2012, “the 29th Inoue prize” by Inoue Foundation for Science in 2013 and “The Kihara prize” from The Genetic Society of Japan in 2016.

During evolution, the number of genes and cell size increased, and the overall complexity of the organism increased along with them. These evolutionary changes are thought to require more ribosomes to support an increased level of protein synthesis. As the result, the genes encoding ribosomal RNA became the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the ribosomal RNA gene repeats (rDNA) are some of the most fragile sites in the chromosome and are linked to cellular functions in yeast and mammals.

A unique gene amplification system of the rDNA has developed to compensate for loss of copies. We revealed the basic mechanism of rDNA amplification. In the mechanism, amplification recombination is induced by inhibition of DNA replication and non-coding transcription. Interestingly, we also found that unstable rDNA induces cellular senescence and shorten the lifespan while stabilized rDNA extends it. I present a hypothesis called “rDNA theory for 

aging”. In the hypothesis, I speculate the rDNA works as a sensor to monitor genome instability and induces cellular senescence that prevents tumorigenesis.

To identify factors that could connect reduced genome stability in rDNA to senescence, we screened ~5,000 strains of a Saccharomyces cerevisiae deletion library and found ~700 genes that were important for the upkeep of rDNA. These included, as expected, genes associated with chromosome organization, DNA repair and recombination. Surprisingly, deletion of many genes not related to genome maintenance had a marked effect on rDNA structure.

Our screening results suggested several genes instrumental in the production of an aging signal. In the absence of some of these genes, the connection between rDNA instability and senescence was lost. I talk about a mechanism that explains how molecular events at the heart of the replication fork induce abnormal rDNA recombination and are responsible for the emergence of an aging signal.​