Gene expression profiling has identified numerous processes altered in aging, but how these changes arise is largely unknown. Here we combined nascent RNA sequencing and RNA polymerase II chromatin immunoprecipitation followed by sequencing to elucidate the underlying mechanisms triggering gene expression changes in wild-type aged mice. We found that in 2-year-old liver, 40% of elongating RNA polymerases are stalled, lowering productive transcription and skewing transcriptional output in a gene-length-dependent fashion. We demonstrate that this transcriptional stress is caused by endogenous DNA damage and explains the majority of gene expression changes in aging in most mainly postmitotic organs, specifically affecting aging hallmark pathways such as nutrient sensing, autophagy, proteostasis, energy metabolism, immune function and cellular stress resilience. Age-related transcriptional stress is evolutionary conserved from nematodes to humans. Thus, accumulation of stochastic endogenous DNA damage during aging deteriorates basal transcription, which establishes the age-related transcriptome and causes dysfunction of key aging hallmark pathways, disclosing how DNA damage functionally underlies major aspects of normal aging.

Introduction The coronavirus disease (COVID-19) pandemic has changed routine clinical practice worldwide with major impacts on the provision of care and treatment for stroke patients. Methods This retrospective observational study included all patients admitted to the Royal Stoke University Hospital in Stoke-on-Trent, UK, with a stroke or transient ischaemic attack between March 15th and April 14th, 2020 (COVID). Patient demographics, characteristics of the stroke, treatment details and logistics were compared with patients admitted in the corresponding weeks in the year before (2019). Results There was a 39.5% (n = 101 vs n = 167) reduction in admissions in the COVID cohort compared with 2019 with more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) 7 vs 4, p = 0.02), and fewer strokes with no visible acute pathology (21.8 vs 37.1%, p = 0.01) on computed tomography. There was no statistically significant difference in the rates of thrombolysis (10.9 vs 13.2%, p = 0.72) and/or thrombectomy (5.9 vs 4.8%, p = 0.90) and no statistically significant difference in time from stroke onset to arrival at hospital (734 vs 576 min, p = 0.34), door-to-needle time for thrombolysis (54 vs 64 min, p = 0.43) and door-to-thrombectomy time (181 vs 445 min, p = 0.72). Thirty-day mortality was not significantly higher in the COVID year (10.9 vs 8.9%, p = 0.77). None of the 7 stroke patients infected with COVID-19 died. Conclusions During the COVID-19 pandemic, the number of stroke admissions fell, and stroke severity increased. There was no statistically significant change in the delivery of thrombolysis and mechanical thrombectomy and no increase in mortality.

The rising incidence of cancer worldwide is causing an increase in the workload in pathology departments. This, coupled with advanced analysis methodologies, supports a developing need for techniques that could identify the presence of cancer cells in cytology and tissue samples in an objective, fast, and automated way. Fourier transform infrared (FT-IR) microspectroscopy can identify cancer cells in such samples objectively. Thus, it has the potential to become another tool to help pathologists in their daily work. However, one of the main drawbacks is the use of glass substrates by pathologists. Glass absorbs IR radiation, removing important mid-IR spectral data in the fingerprint region (1800 cm−1 to 900 cm−1). In this work, we hypothesized that, using glass coverslips of differing compositions, some regions within the fingerprint area could still be analyzed. We studied three different types of cells (peripheral blood mononuclear cells, a leukemia cell line, and a lung cancer cell line) and lymph node tissue placed on four different types of glass coverslips. The data presented here show that depending of the type of glass substrate used, information within the fingerprint region down to 1350 cm−1 can be obtained. Furthermore, using principal component analysis, separation between the different cell lines was possible using both the lipid region and the fingerprint region between 1800 cm−1 and 1350 cm−1. This work represents a further step towards the application of FT-IR microspectroscopy in histopathology departments.