Ask the Expert Interview: Malene Hansen, PhD, on Autophagy and Aging Research

Building a legacy in any field of research takes intense dedication and Malene Hansen has set a crucial example of what’s possible with a clear scientific focus and grant support along the way. AFAR connected with Dr. Hansen to learn more about her fascinating research that focuses on how cells interact and self maintain, a process called autophagy. Dr. Hansen continues to be a global leader in the field of aging research, recognized throughout her career including receiving multiple AFAR grants. Dr. Hansen is the Chief Scientific Officer and a professor at the Buck Institute for Research on Aging, and over the years has been an avid mentor to postdoctoral scholars and graduate students.

How have molecular insights changed our understanding of aging and the progression of age-related diseases?

When I first entered geroscience research as a postdoctoral researcher 20 years ago, there was a lot of focus on identifying new longevity genes. Research of these genes later highlighted a number of highly conserved cellular mechanisms that each contributes to organismal aging. A prominent example to this end is a recycling process called autophagy, which is the focus of our lab’s research. More recently, we have begun to learn more about how such cellular mechanisms not only affect the inside of the cell itself, but also induce signaling events between cells that can influence aging and age-related diseases. It will be an important objective for the future to better understand how changes in basic, cellular processes are communicated to other cells, tissues, or organs, and how such socalled inter-tissue signaling contributes to aging and age-related diseases.

What is the importance of the autophagy process and why is it the key focus of your research?

Our cells have a remarkable capacity to recycle or self-digest (‘auto-phagy’) parts of itself, e.g, accummulating waste products like damaged cell components and aggregated proteins. The cell induces this highly conserved process to keep themselves in a healthy and functional state. In turn, dysregulated autophagy has been linked to numerous diseases, including infection and immunity, neurodegeneration, heart disorders and cancers. Interestingly, we and others have found that longer-lived model organisms seems to boost autophagy in a seemingly beneficial manner, perhaps helping remove toxic materials that normally accumulate over time. Our lab’s research focus on understanding the role and regulation of autophagy in aging, as we believe we can learn important biology that is relevant to our understanding of aging and age-related diseases, including providing new avenues for combating these disorders.

You have the unique situation of receiving four AFAR grants at various stages of your career. Why is this kind of support so vital to advance the research process, particularly for emerging investigators?

I am very grateful to AFAR’s support of my research for over 15 years with four AFAR research grants (i.e., Ellison Medical Foundation/AFAR Senior Postdoctoral Fellows Grant (2005), an AFAR Research Grant for Junior Faculty (2009), a Julie Martin Mid-Career Award (2014), and a Breakthrough in Gerontology Award (2020)). These grants were crucial for starting my independent career, as well as to serve as ‘seed’ grants/ideas for obtaining long-term, federal funding. Importantly, they also helped move our research in new directions. For example, while our lab has primarily used the nematode C. elegans for our investigations, the Julie Martin Mid-Career Award facilitated implementation in our lab of mammalian cell cultures as a model system, which is extremely useful for investigating a cellular and very mechanistic process like autophagy. Having support to get your ideas off the ground with strong preliminary data and the flexibility to pursue new directions is absolutely critical, especially for emerging investigators.

In addition to the financial support, AFAR has also helped facilitate other aspects of my career. For example, I attended AFAR annual meetings that helped grow my scientific network. AFAR also provided the opportunity to help review other investigator’s grants; as an early-stage investigator, this was a great learning and mentoring experience that I highly recommend.