Contributed by Sancy Leachman, MD, PhD, Oregon Health & Science University
The Friday and Saturday Montagna sessions were spectacular – both because of the quality of the presentations and because of the audience engagement! The speakers could barely get off the stage because of all the questions. It’s impossible for me to capture the enthusiastic tone of the meeting.
It’s also remarkable that the meeting, though centered on aging, is proving to be a study in the nature of scientific discovery and the relationship between discovery and scientific tools. I suppose it has always been this way; the wheel had to be discovered before a larger world could be explored. In the case of this year’s Montagna, although the specific topic of aging is finite, the principles of discovery that are being applied are enduring.
For example, Howard Chang began the meeting with a stated goal of understanding how the activities of thousands of genes are coordinated to create the process and variability of aging. As part of his investigations, he has developed tools to use chromatin itself as a “GPS device” to show which genomic areas comprise an individual’s personal “regulome.” This personalized regulome approach has identified active regulatory areas that are not translated into protein, including long non-coding RNAs. Not long ago, there existed a dogma that these non-coding areas of the genome, including pseudogenes, were functionally “dead” pieces of redundant DNA. Howard’s studies show that these genes are very much alive and functioning, and have also helped to “bring to life” this new field of investigation. A similar theme of life and death of a dogma was articulated by Judith Campisi, who reported her latest thinking on the process and role of cellular senescence. She showed compelling data, proving that senescent cells are not just passive, past-their-prime bystanders, merely sitting quietly in place (as was once believed). She showed that these senescent cells produce a host of SASP (senescent-associated secretory protein) molecules that dramatically impact the tissue microenvironment. Ultimately, she asked a provocative question: if these senescent cells could be selectively removed, would the tissue environment remain younger and healthier?
Additional “dogma-bashing” was enabled by the development and utilization of powerful investigational tools and approaches. Valentina Greco showed amazing video coverage of hair follicle regression via consumption of apoptotic cells – not by phagocytic hematopoietic cells as previously believed – but by their neighboring keratinocytes. Gary Fisher showed amazing (3-D, rotating, second harmonic generation) images that revealed physical changes in aging dermis as well as responses of the skin to an injectable cosmetic filler. And Vera Gorbunova showed how the naked mole rat (a remarkable creature that manages to lives longer without cancer than other vertebrates on the planet), has been used to identify high-molecular weight hyaluronan as a potential anti-aging agent. Clearly, these tools are enhancing our ability to test critical hypotheses, but just as the wheel (and boat) permitted discovery that the world was round, the tools presented at Montagna expand our ability to challenge dogma, see new horizons, and construct better hypotheses. Remarkably, as we study the process of aging, death, and immortality, we see the timeless principles of discovery as well.