What inspired you to pursue aging research?
At the crossroads between our body and the outside world, skin is a daily visible reminder of how our body is aging. My laboratory has long been fascinated by how our body surface is able to rejuvenate itself throughout life. As we learned how this happens in youth, we naturally became interested in how the regenerative potential of the epidermis and its notable appendages, the hair follicles, slows down with aging. My laboratory is also interested in the consequences of a life-long barrage of inflammation, wounds, mechanical stress, and other assaults to the skin, and whether there might be ways to prevent and/or erase the damage.
In your view, what does AFAR mean to the field, and what does it mean, for you, to receive an AFAR grant now?
AFAR offers researchers interested in aging research the opportunity to think big and outside the box. In receiving this Discovery Award, I am able to explore uncharted territory in the field of aging research. Some years ago, my laboratory discovered that the cells that make and repair the body surface retain memories of an acute inflammatory experience, enabling them to learn from past encounters and respond to future stresses more rapidly and effectively. Although these memories can be beneficial, for example, in more quickly healing wounds, they can also be detrimental, for instance, in contributing to chronic inflammatory disease. Our AFAR grant allows us to study how aging affects the ability of these skin cells to mount and recall memories and explore whether such knowledge might be helpful in the future to devise ways to enhance a tissue’s ‘good memories’ and eliminate its ‘bad ones.’
What is exciting about your research’s potential impact?
Chronic inflammation is on the rise in our aging population. Treatments are typically prolonged use of immune suppressive drugs, which often result in relapse when treatments are stopped. Our studies in mice suggest that the heart of chronic disease may reside in the tissue stem cells that acquire long-lasting epigenetic memories of an acute inflammatory experience that endow the tissue to respond faster and quicker to future stressful experiences. While beneficial for wound repair, this can be deleterious for chronic inflammatory disorders. Dr. Fuchs’ laboratory hopes to identify the mechanisms underlying aging, stress, and memories and, in so doing, devise ways to enhance a tissue’s ‘good memories’ and eliminate its ‘bad ones.’
How would you describe your research to a non-scientist?
Our skin is our body’s visual reminder of aging. My laboratory studies the cells of the skin that have the extraordinary multifaceted ability to rejuvenate the body surface (every four weeks, you’ve got a brand new epidermis), make hair, and heal wounds. These very special cells, called ‘tissue stem cells', reside in specific places in the skin (hair follicle, sweat gland, epidermis) and through their interactions with their local tissue cells, they know exactly what their tissue task is and when to perform it. My laboratory discovered that tissue stem cells have a way of cataloguing their lifelong experiences with stressful situations, including wounds and acute inflammation, which enables them to respond quicker and more robustly to future stress. In wounding, this is a benefit, as the wound heals faster; however, for inflammation, it is a detriment and can lead to chronic disease. The discoveries we’ve made by studying this process in the skin appear to be broadly applicable to other tissues, each of which have their own tailor-made tissue stem cells.
We now want to address: What happens when our tissue stem cells acquire a life of experiences? Could this be a contributing factor to why our tissues lose fitness as we age? If so, what can we do to control the process of tissue memory?
