Life is a cycle of aging and rejuvenation

Life is a cycle of aging and rejuvenation

Tall cherry trees on the premises of the National Institute of Genetics blossom and grow new leaves each year. How is this continuity maintained? The question comes from the same place as Prof. Takehiko KOBAYASHI’s interest in genome, the blueprint of life that has continuously existed for over three billion years.

Aging and rejuvenating at the same time

The yeast species is a model organism whose genomic decoding is complete. It is a unicellular organism and also the simplest life form which ages. Its reproduction is by budding, a kind of cell division. One cell divides about 20 times and dies. After the 10th cell divisions or so, the cell starts becoming larger in size as the vacuole, in which waste products are contained, becomes larger. The doubling time, which is one every two hours at first, drops to about one every eight hours in the end.

Aging is basically decaying. “It’s natural. No one can stop it,” says Dr. Kobayashi, “What is interesting about yeasts is that while the mother cell continues aging, it gives birth to a daughter cell, which undergoes ‘resetting’ and becomes a new cell. The daughter cell can still divide 20 times or so even after the mother cell has stopped.”

“Resetting” happens not only in yeasts but also in stem cells and germ cells in the human body. Individuals continue to age, but these cells continue to be rejuvenated without fail through repeated cell divisions. “Like yeasts, humans undergo continual resetting at the cellular level.”

Aging as a positive phenomenon

In around 1996, the gene that causes the accelerated aging disease (DNA-repair-deficiency disorder) was identified. The average life expectancy of patients suffering from this hereditary disease is a very short 48 years. Once it was revealed that the gene responsible for the disease was also involved in the aging of yeasts, the yeast species began to draw greater attention than ever before as a model organism for research into human aging. Yeasts are an intriguing and highly useful species for researchers: it enables them to produce mutant strains and compare them with normal ones with genetic techniques.

Among the mutant strains of yeasts that Dr. Kobayashi has produced is a strain lacking the fob1 gene whose aging process is extremely slow. It lives 60% longer than wild strains and divides about 30 times before dying. Dr. Kobayashi used the mutant strain in his research to elucidate the molecular-level mechanism of aging and rejuvenation and find out “why it’s necessary to age and what would happen if living organisms didn’t age.”

As he pursued his research, Dr. Kobayashi discovered that the strain lacking the fob1 gene does in fact age but the timing of its death was simply delayed. He found out that after 20 or more cell divisions the strain had frequent cellular abnormalities such as mutations in the genome. He believes that aging is a system that actively kills cells before abnormal ones are born. He says, “Cancer has become one of the top death causes since the human life expectancy has become longer. A merely longer life expectancy doesn’t guarantee greater happiness in life. Making sure to prevent cellular abnormalities or diseases is just as important and necessary as living longer. We must realize both to happily live a long life.”

Personal reasons for pursuing greater knowledge

Dr. Kobayashi was first interested in aging as his personal issue. According to him, “research results basically depend on how much each researcher wants to know. While research techniques can be taught, passion for research must come from individual motivation, how much one wants to clarify some mysterious phenomenon. In my case, I just took the bait that was right before my eyes.” For him, molecular biology has always been familiar in that “I also have genes”; it has also been mysterious. With Dr. Kobayashi, who recognizes with a smile that curiosity can be manifested in a myriad of ways, young researchers will surely be able to pursue their own curiosity and develop unlimited potential.

(Interviewed by Leave a nest Co.,Ltd in 2010)