Shinya Yamanaka

Background

Shinya Yamanaka is a Japanese physician and stem-cell scientist who discovered how to turn ordinary adult cells back into an embryonic-like state, creating what are called induced pluripotent stem cells, or iPSCs. By adding just four genes, later known as the Yamanaka factors, to a mature cell, he showed in 2006 that its developmental clock could be reset so that it regained the ability to become almost any cell type in the body. For this discovery he shared the 2012 Nobel Prize in Physiology or Medicine with the British biologist John Gurdon. Yamanaka trained as a physician, earning his medical degree from Kobe University in 1987 and initially pursuing orthopedic surgery. Finding himself better suited to research, he completed a PhD at Osaka City University, undertook postdoctoral training at the Gladstone Institutes in the United States, and eventually established his laboratory at Kyoto University.

Induced pluripotent stem cells

Embryonic stem cells can become any cell type, but obtaining them requires destroying an embryo, which raises ethical and practical problems. Yamanaka asked whether a mature cell could be reprogrammed back to that flexible state. Rather than test genes one at a time, his laboratory selected two dozen candidate genes active in embryonic stem cells and narrowed them down. In 2006 his team, with the graduate student Kazutoshi Takahashi, reported that just four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, could reprogram adult mouse skin cells into cells that behaved like embryonic stem cells, and the following year the group and others achieved the same feat with human cells. The achievement demonstrated that a cell's identity is not fixed but is maintained by a small set of master regulators, and that this identity can be reset. Because iPSCs can be made from a patient's own tissue, they sidestep both the ethics of embryo use and the risk of immune rejection.

Applications in medicine

iPSCs quickly became a standard tool across biology. They allow scientists to grow a patient's disease in a dish, model conditions such as Parkinson's and heart disease, and screen candidate drugs. Clinicians have begun testing iPSC-derived cells as treatments, including retinal cells for macular degeneration and dopamine-producing neurons for Parkinson's disease, and the cells are central to advances in organ regeneration and tissue engineering. Yamanaka helped establish an iPSC stock program in Japan to bank matched cell lines for clinical use. He is a professor and founding director of the Center for iPS Cell Research and Application at Kyoto University and has been a senior investigator at the Gladstone Institutes in San Francisco.

Reprogramming and aging

Yamanaka's factors turned out to have a second, unexpected significance for the biology of aging. Full reprogramming erases a cell's identity, but researchers found that applying the factors briefly, a strategy called partial or transient reprogramming, can make old cells look and function younger while keeping their identity intact. In cell and animal studies this partial reprogramming reverses some measures of biological ageTermBiological ageAn estimate of organism or tissue state relative to typical aging patterns, usually inferred from biomarkers rather than birthdays.In glossary →, including certain changes counted among the hallmarks of agingArticleHallmarks of AgingA shared framework that organizes aging into interconnected biological processes, giving longevity research a common map of what to measure and target.Read entry →. This insight launched a wave of investment in rejuvenation research. The company Altos LabsCompanyAltos LabsBiotechnology company launched in 2022 with reportedly around three billion dollars to pursue cellular rejuvenation and reverse aspects of aging through epigenetic reprogramming.Company →, founded in 2022 with several billion dollars in funding, was built largely around reprogramming biology, and Yamanaka joined it as an unpaid senior scientific adviser while remaining at Kyoto. Other ventures, including NewLimitCompanyNewLimitA longevity biotech co-founded by Coinbase chief Brian Armstrong that pairs partial epigenetic reprogramming with machine learning to restore youthful gene expression.Company →, and academics such as David SinclairPersonDavid SinclairAustralian-born Harvard Medical School geneticist known for research on sirtuins, NAD+, and the information theory of aging, and for his bestselling book Lifespan.Person → are pursuing the same idea, though whether transient reprogramming can be made safe and effective in humans, without raising cancer risk from factors such as c-Myc, remains an open question. Beyond the Nobel Prize, Yamanaka has received the Lasker Award, the Wolf Prize, the Millennium Technology Prize, and a Breakthrough Prize in Life Sciences.

Related pages

What links here

• Altos Labs
• David Sinclair
• NewLimit
• Steve Horvath