From the Campisi Lab
The Campisi laboratory continues to discover new ways that senescent cells cause aging -- most recently skin aging. Cellular senescence is an anti-cancer mechanism that permanently prevents cells from dividing. The Campisi group pioneered the idea that the senescence response is a double-edged sword: it protects us from cancer early in life, but can promote aging and age-related disease late in life. The pro-aging effects of senescent cells are due largely to the fact that they accumulate with age and secrete proteins that cause chronic inflammation, which causes or contributes to virtually every major age-related pathology.
In collaboration with the Melov laboratory, postdoctoral fellow Michael Velarde showed that mitochondrial oxidative stress causes cells in the epidermis (outermost skin layer) to undergo senescence. Michael and Jim Flynn, a postdoctoral fellow in the Melov group, showed that this senescence response is accompanied by thinning of the epidermis, a hallmark of aging skin. Michael's paper reporting these results will appear soon in the journal Aging.
What can be done about the accumulation of senescent cells and their pro-aging effects? Postdoctoral fellow Remi-Martin Laberge, in collaboration with the Hughes laboratory, spearheaded the first high-throughput screen for drugs that either selectively kill senescent cells or suppress their secretion of pro-inflammatory proteins. With help from postdoctoral fellow Peter de Keizer, former graduate students Lilli Zhou and Adam Freund, former fellow Francis Rodier, consultant Pierre Desprez and fellows in the Hughes and Kapahi laboratories Melissa Sarantos and Su Liu, Remi identified cortisol and corticosterone as potent suppressors of the deleterious secretions of senescent cells. In addition to providing novel insights into how the deleterious effects of senescent cells are controlled, this pioneering drug screen opens the way for discovering new anti-aging therapeutics aimed at eliminating senescent cells or their inflammatory secretions. Remi's paper received favorable reviews, and is awaiting final acceptance for publication.
Last but not least, Marco Demaria was a visiting graduate student from Italy last year. In December he returned to Italy and successfully defended his thesis. Happily, he is now back in the Campisi lab as a postdoctoral fellow. He is working on a new mouse model developed by the Campisi laboratory and collaborators in the Hoeijmakers laboratory in Rotterdam (Holland). This model allows senescent cells to be eliminated due to a genetic manipulation, and will be a 'gold standard' against which to judge the efficacy of drugs that hopefully do the same.