Westendorp, R. | bioRxiv Science

bioRxiv2021

Deep Learning Shows Cellular Senescence Is a Barrier to Cancer Development

Cellular senescence is a critical component of aging and many age-related diseases, but understanding its role in human health is challenging in part due to the lack of exclusive or universal markers. Using neural networks, we achieve high accuracy in predicting senescence state and type from the nuclear morphology of DAPI-stained human fibroblasts, murine astrocytes and fibroblasts derived from premature aging diseases in vitro. After generalizing this approach, the predictor recognizes an increasing rate of senescent cells with age in H&E-stained murine liver tissue and human dermal biopsies. Evaluating corresponding medical records reveals that individuals with increased senescent cells have a significantly decreased rate of malignant neoplasms, lending support for the protective role of senescence in limiting cancer development. In sum, we introduce a novel predictor of cellular senescence and apply it to diagnostic medical images, indicating cancer occurs more frequently for those with a lower rate of senescence.

cell biology↗

bioRxiv2017

Centenarian Hotspots in Denmark

BackgroundThe study of regions with high prevalence of centenarians is motivated by a desire to find determinants of healthy ageing. While existing research has focused on selected candidate regions, we explore the existence of hotspots in the whole the Denmark, which is a small and homogeneous country.\n\nMethodsWe performed a Kulldorff spatial scan across the whole of Denmark, searching for regions of birth and regions of residence at age 71 where a significantly increased percentage of the cohort born 1906-1915 became centenarians. We compared mortality hazards for the hotspot regions to the rest of the country by sex and residence at age 71.\n\nResultsWe found a birth hotspot of 222 centenarians, 1.37 times more than the expected number, centered on a group of fairly remote rural islands. Mortality was lower for those born in the hotspot, and the advantage was strongest in those born and remaining in the hotspot. At age 71, we found one primary hotspot with 1.39 times the expected number of centenarians, located in the generally high-income suburbs of the Danish capital.\n\nConclusionWe identified a Danish centenarian birth hotspot that persisted over a period of at least 30 years. Exactly what drives the appearance of this birth hotspot is unknown, but selection may explain hotspots based on residence at age 71.

epidemiology↗