William Mair
William Mair - PhD
Glenn/AFAR Breakthroughs in Gerontology Award - 2017
William Mair

William Mair - PhD

Assistant Professor, - Harvard T.H. Chan School of Public Health
Massachusetts, USA


Glenn/AFAR Breakthroughs in Gerontology Award - 2017

The role of RNA splicing in TORC1 physiology in mammals

As we age, our capacity to maintain cellular homeostasis decreases. That puts us at an increased risk for a plethora of chronic conditions. Therefore, maintaining cellular homeostasis is essential for healthy aging and longevity.

At its most basic level, cellular homeostasis is maintained by the ability to correctly convert the information encoded in our genomes into the proteins and enzymes required for correct cellular function. One of the surprises of the human genome project was that, despite the complexity of our cells and tissues, we only have around 20,000 protein-encoding genes.

A key mechanism that generates the complexity of our proteome (the variety of proteins in our cells) is a process called “Alternative RNA Splicing.” This process is an important step in the central dogma that can generate many alternative proteins from one gene. These variants can have different roles in different cell types. Although such a system gives us complexity not seen in simpler organisms, it is also vulnerable to age-related dysfunction.

Dr. Mair is studying how dysfunction of the RNA-processing machinery can drive the aging process and cause disease. He is also exploring how mechanisms that can slow aging, such as dietary restriction, do so in part by maintaining splicing fidelity. His research is driven by these central questions: Why are we more likely to get chronic diseases when we are old than when we are young? What goes wrong in cells and tissues to increase risk? Is this decline inevitable, or can we reverse it to bring healthy years to the elderly?

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