Insights Related to Senescence and the Aging Microenvironment
Researchers with the Fred Hutch OAC Project, generated a senescence associated secretory phenotype (SASP) atlas of human colon fibroblasts, which revealed insights into potential driver proteins involved in senescence-associated disease (such as colorectal cancer).
By performing senescence profiling of monoclonal gammopathies, researchers with the University of Michigan OAC Project showed that failure to activate tumor-specific paracrine senescence plays an important role in disease progression.
Dr. Taihao Quan et al. with the other University of Michigan OAC Project showed that CCN1 is elevated in human dermis (i.e., middle layer of skin) by UV irradiation and accumulates in the dermal extracellular matrix (ECM). Their findings “suggest that accumulation of CCN1 in the dermal ECM is expected to progressively promote the aging of the dermis and thereby negatively impact the function of the dermis.”
Mechanistic Effects of Aging on Cell States and Cancer Development
Dr. Carla Kim et al. with the Harvard Medical School OAC Project showed that age-associated loss of histone H3 lysine 9 di-methylation (H3K9me2) alters the regenerative equilibrium between lung alveolar and bronchiolar progenitor cells. According to the authors of the study, “These findings indicate that during aging, the epigenetic regulation that coordinates lung progenitor cells' regenerative responses becomes dysregulated, aiding our understanding of age-related susceptibility to lung disease.”
Researchers with the MSKCC OAC Project revealed how genetic alterations, cell-state transitions, and microenvironmental remodeling converge to drive early pancreatic cancer progression.
Dr. Monte Winslow et al. with the Stanford University OAC Project showed that aging represses oncogenic KRAS-driven tumor initiation and growth in preclinical models of lung cancer.
Identification of Cancer Vulnerabilities
Researchers with the UCSD OAC Project showed that AML cells are resistant to proteasome inhibitors via activation of HSF1 and autophagy. They also found that blocking HSF1 or autophagy sensitizes AML to proteostasis disruption.