Adult tissue stem cells (SCs) play an important role in tissue homeostasis and regeneration in multicellular organisms. With aging, these cells decline in their capacities such as regeneration, proliferation, and differentiation, leading to disruption of tissue homeostasis in systemic organs. The senescence-associated secretory phenotype (SASP), that is, senescent cells secrete various inflammatory factors, has been implicated in the promotion of chronic inflammation and organismal aging. However, little is known about the common molecular mechanisms underlying SC aging and their influence on systemic aging. Here we show that dysregulation of the DNA damage response (DDR) is a common molecular mechanism of SC aging and induction of premature aging in intestinal stem cells (ISCs) promotes senescence-like phenotypes in remote multiple organs, including the skin. We identified a transcription factor that is commonly downregulated both in aged mesenchymal stem/stromal cells (MSCs) and hematopoietic stem/progenitor cells (HSCs), and found that repression of this gene impairs DDR capacity. Deficiency of the gene in ISCs induced not only loss of DDR capacity and inflammation, as in the aged intestine in vivo, but also age-related dysfunctions in the remote brain, kidneys, and skin. Furthermore, deficiency of the gene in epidermal stem cells (EpSCs) induced loss of DDR capacity, marked reduction of hair, accumulation of subcutaneous fat, and reduction of collagen, as in aged skin. These results suggest that the gene is critical for the common molecular basis of SC aging and that its regulation enables us to investigate the inter-organ influences of specific SC aging.

ESDR559 - Induction of tissue-specific premature stem cell aging promotes senescence-like phenotypes in remote multiple organs

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.