CMU Professor Ao-Lin Hsu of Center of Excellence for Healthy Aging Published Research Findings in Science Advances
Date：October 22, 2020
A major breakthrough in the research of longevity gene. CMU Professor Ao-Lin Hsu of Center of Excellence for Healthy Aging led a research team that discovered the genes that can control the life clock, and found the molecular mechanisms of HSF1 and HSB1 proteins in delaying aging and prolonging life span. Their research findings “HSB-1/HSF-1 pathway modulates histone H4 in mitochondria to control mtDNA transcription and longevity” was published in the prestigious journal Science Advances.
In the past 16 years, CMU Center of Excellence for Healthy Aging has been working hard to find the longevity genes and aging genes that can control the life clock and the speed of human aging. The research team was trying to understand the roles of these genes in regulating the speed of aging at the cellular and molecular levels. Now the team discovered that when HSF1’s inhibitory protein HSB1 is eliminated, the aging speed will significantly delay and the life span of the animals will be prolonged. Besides, the expression of histone H4 in the cells of these animals is higher than usual. Interestingly, histone H4 is one of the main components of nucleosome in the nucleus, so it is generally believed to appear in the nucleus only.
However, Professor Ao-Lin Hsu’s team further discovered that in the cells of these long-lived animals, histone H4 would transfer to appear in the mitochondria, and bind with mitochondrial DNA (mtDNA) and regulate the gene expression of mtDNA to affect mitochondrial function. In addition, HSF1/HSB1 and other longevity genes can also increase the stress resistant of cells and delay aging with the same method. This research not only revealed the molecular mechanism of HSF1 and HSB1 proteins in delaying aging and prolonging lifespan, but also provided a latest evidence that histone H4 can transfer to mitochondria under certain conditions to perform different functions.
In the application of translational medicine, this research provides an excellent benchmark for the development of anti-aging drugs in the future. Professor Hsu expects that if an effective HSB1 protein inhibitor can be developed in the future, there might be a possibility to develop a new anti-aging strategy that can prolong the “healthspan” of human beings to achieve the goal of “healthy aging.”