Montagna 2014: An immortal organism?

Contributed by Sancy Leachman, MD, PhD, Oregon Health & Science University

 

At Montagna this year, I experienced an intellectual excitement surrounding the discovery of aging processes and mechanisms, but also appreciated that this field is driven by a particular human urge to understand and attain longevity, and perhaps immortality. Both our minds and hearts were stimulated to support discovery of ways to prevent and treat aging disorders such as Werner and Hutchinson-Guilford Progeria syndromes, as discussed by Ray Monnat and Maria Eriksson. A full program on Sunday explored innovative strategies to prevent and reverse skin aging, including opportunities in epigenetic regulation (Vladimir Botchkarev), targeted telomere-based methods (Calvin Harley), mTOR pathway agents (Silvio Gutkind), and even a clever strategy of DNA “photoprotection” with biomimetic acyclothymidine dinucleosides (Abbas Raza). Rosemarie Osborne also reported on the use of powerful transcriptional profiling tools to understand the expression changes that occur during aging in normal human skin.  And finally, the afternoon session reached a zenith with an industry-led panel discussion on future directions. The panel discussion was so powerful because it was preceded by all of the scientific presentations and discussions. This priming effect led to a productive dialogue to explore opportunities for the development of new skin products through fair and productive collaboration between academia and industry.  It was magnificent!

 

Just as magnificent as the science, however, was the conference itself. At 63 years of age, the conference is entering a more mature era and may be a relevant metaphor for the aging theme. At the conference banquet, Molly Kulesz-Martin and Barbara A. Gilchrest provided some history of the conference, which was begun by Bill Montagna to catalyze scientific progress toward improved skin health. They also thanked all of the attendees for continuing the tradition of Montagna. In its 63 years, Montagna might be considered almost organismic in nature. It is composed of a relatively stable population of participants, some of whom have attended more than 20 of these meetings. We had several senior leaders of dermatologic science who attended this year, including Jon Hanifin, Jerry Krueger, John Voorhees, Sewon Kang — individuals who provide a lifetime of experience, stability, quality and relevance to the meeting. In addition, the conference hosts individuals with a wide variety of expertise, including basic cellular and molecular biologists, physical and medicinal chemists, bioengineers, photobiologists, physicians, industrial scientists, businessmen and more. Finally, attendees also vary in age (senescence?) and level of experience, including undergraduate, medical and graduate trainees, young investigators, and senior physicians and scientists. After the banquet, I roasted marshmallows around a firepit with residents, faculty, and a faculty recruit. It occurred to me that we have a solution to the mortality problem at the group level. By bringing in young, enthusiastic, and diverse expertise, we not only maximize the impact of the science, but our work can become in some ways immortal. What an appropriate holy grail!

 

Disclaimer: I can’t deny this blog entry is a bit “corney-fied,” but what do you expect from a dermatologist who’s been at a brain-intense conference all weekend!

Montagna 2014: The quest for the fountain of youth

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.