Inside AFAR
Inside AFAR

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Jan 23
4:04 pm

Grantee Spotlight Interview: William Mair View MoreBACK


AFAR’s grant programs in the biology of aging are central to our mission to support and advance healthy aging through biomedical research. At leading institutions nationwide, our grantees hard work, ingenuity, and leadership are advancing cutting-edge research that will help us all live healthier, longer. AFAR grantees are making this the age of aging better.

In this Grantee Spotlight interview, William Mair, PhD, shares what inspired him to enter the field of aging research and what impact he hopes his research will make thanks to AFAR’s support.

William Mair - PhD

Assistant Professor

Harvard T.H. Chan School of Public Health

Glenn/AFAR Breakthroughs in Gerontology Award - 2017

What inspired you to pursue aging research?

I first got interested in aging research as aging is an evolutionary biology paradox – if aging is so detrimental to an organism, why does it exist? Most people’s first take on this question is either: aging exists because, like machines, bodies must undergo some inevitable decline, or, aging exists because it’s better for the species if the old die off to make way for the young. Neither of those options fits with evolutionary theory, which makes aging such an interesting topic! In fact, aging exists because, during evolution, very few individuals survived the harshness of their reality long enough to become old – so any mutation that gave them some benefit in their youth was favored by selection, even if it caused problems in old age. What we are seeing now in human populations is what happens when we remove so many of the things that used to kill our ancestors off in their youth - now those hidden problems become exposed, the population ages, and we see huge increases in diseases of old age our forefathers didn’t live long enough to suffer from. Although my lab is not an evolutionary biology lab, the questions that interest us are routed in those concepts – now public health has exposed diseases previously hidden, what can we do to prevent them?

In your view, what does AFAR mean to the field, and what does it mean, for you, to receive an AFAR grant now?

AFAR has supported me and so many of my peers throughout our careers as we try and understand the mechanisms that link old age to disease risk. This AFAR BIG award is particularly timely for my group, as it will allow us to develop a new area of research for us – the links between RNA splicing and aging – and test whether observations we have made in invertebrate systems are conserved in mammals and might be exploited to reduce human disease risk.

What’s exciting about your research’s potential impact?

Aging results from a decreased capacity to maintain cellular homeostasis with age, leading to increased risk for a plethora of chronic conditions. At its most basic level, cellular homeostasis is maintained via fidelity of the central dogma: DNA>RNA>Protein, e.g. 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 thousand 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’, which is a key 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 such as bacteria, it is also vulnerable to age-related dysfunction. We study how dysfunction of the RNA processing machinery can drive the aging process and cause disease, and how mechanisms such as dietary restriction, that can slow aging, do so in part by maintaining splicing fidelity.

In three sentences, how would you describe your research to one of your grandparents?

We study the basic biology of the aging process, driven by the central question: 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 overall risk, and is this decline inevitable or can we reverse it to bring healthy years to the elderly?

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