Photo courtesy of the Buck Institute for Research on Aging

Judith Campisi, who passed away on January 19th of this year, was arguably the most influential researcher on cellular senescence, the permanent cessation of replication in previously replicative cells, and its implications since Moorhead and Hayflick discovered the phenomenon more than 60 years ago. When I first met Judy, the name by which everyone knew her, in about 1990, the aging biology field was still split over whether cellular senescence even occurred in actual organisms or whether it was merely a “culture artifact,” a phenomenon found only in laboratory tissue culture without any relevance to aging in living organisms. Judy was convinced of the former, and when her lab developed the first marker for senescent cells, now known as senescence-associated β-galactosidase, and found that these cells became increasingly common in skin samples from increasingly older individuals [1], that issue was settled once and for all. What was not settled was the importance of these cells for normal aging. Judy was not only a gifted experimentalist; she was a deep thinker about aging with a sophisticated appreciation of how evolution could mold cellular phenomena to adaptive organismal advantage. She appreciated that replicative senescence could be an effective tumor suppression mechanism but noted that it could also inhibit tissue repair and regeneration in later life. In the language of evolutionary biology, it was antagonistically pleiotropic [2]. Her lab later discovered another mechanism of antagonistic pleiotropy, the senescence-associated secretory phenotype or SASP [3], which explained how cells which are rare even at the latest ages could have tissue-wide disruptive effects and could even become cancer-promoting in late life but could be beneficial early on via its role in wound healing [4].

Campisi was New York born and bred, receiving both her BA and PhD from the State University of New York Stonybrook with a break in her education while she toured the country singing in a folk music band. Her PhD research on sea urchin fertilization was published in Science and Nature, an outstanding start to an outstanding career. She moved on to study cell cycle dynamics as they relate to cancer with Arthur Pardee at the Dana Farber Cancer Institute in Boston, crediting him with teaching her how to be a good mentor. She remained close friends with Pardee from then on and never visited Boston without stopping to see him. She started her own laboratory at Boston University Medical School where she began her studies of cell senescence and where her interest in their relation to aging biology blossomed. From Boston, she moved to the west coast, taking a position at the Lawrence Berkeley National Laboratory, eventually moving from there across the Bay to the Buck Institute for Research on Aging, where she remained from 2002 until her death.

Despite her international reputation, her ground-breaking discoveries, her many awards, and more than 120,000 citations of her work, Judy was always focused on science rather than personal achievements. She was utterly devoid of hype, something we might all learn from these days. Science was what motivated her and what excited her most. It excited her so much that her friends learned not to put their lives at risk by talking science with her while she was driving.

Judy had many gifts that made her an exceptional scientist and human being. She had the gift of clarity. She thought clearly, spoke clearly, and wrote clearly. Consequently, she was always in high demand as a conference speaker, as a writer of review papers, and as an explainer of science to lay audiences. She also had the gift of what I call “appropriate skepticism,” never too quick to believe, nor too quick to dismiss, novel ideas or results, whether they came from her own lab or from someone else’s. She had a gift for asking the right question in the right way to make it experimentally tractable. One right question she asked was “why do mouse embryonic fibroblasts (MEFs) senesce after many fewer population doublings than human fibroblasts even though they have much longer telomeres and constitutively express telomerase?” Suspecting it might be an artifact of culture conditions, her lab grew MEFs under physiological (3%) rather than ambient (20%) oxygen and discovered that MEFs did not senesce early in physiological oxygen, thus uncovering oxygen sensitivity as a critical difference between mouse and human cells [5]. That finding has improved the translatability of experiments with MEFs ever since.

Another gift Judy had, which was evident from the outpouring of posthumous tributes worldwide, was the gift of friendship. She made, and kept, friends. She expected people to be as open and honest as she was and as accepting of thoughtfully constructive criticism as she was. She had friends in science, friends in dance and music, friends in wine (one of her lasting passions), and friends from all of the many facets of her extraordinary life.

One gift Judy did not have was the gift of sleep. It may be why she and I bonded so quickly—our shared affliction of insomnia. It took us a while to discover that no matter what time of day or night we emailed one another, a reply came right back. I remember one time even mentioning that it was good to finally get an email from her during normal waking hours. “It might be normal waking hours if I were in California,” she said, “but I’m not. I’m in Sicily. It’s 2:30 in the morning here.” Each time our travel schedules by happenstance overlapped so we could actually meet in person, we would share a meal and a bottle of wine, and we would also share any new tips we had seen that were supposed to ameliorate insomnia. None ever seemed to work. “I live in a permanent state of jet-lag,” Judy used to say.

When good friends are gone for good, “returned to stardust” as Carl Sagan used to say, it is sometimes a surprise to discover what you miss most about them. I miss Judy’s clarity and scientific insight, for sure, but I think what I miss most is those 2:30 a.m. emails.