Research Roundup: Genetics of People Older than 105

 

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

Genetics of People Who Live 105 or Older

A new study of 81 semi-supercentenarians—people 105 years of age or older—and supercentenarians—110 years or older from across Italy, were studied by researchers from the University of Bologna, Italy and Nestle Research in Lausanne, Switzerland. They compared genetic data from these extraordinary agers to 36 healthy people from the same region whose age, on average, was 68 years. Blood samples were drawn and whole-genome sequencing was performed. They then compared their data with another previously published study that analyzed 333 Italians over 100 years of age and 358 people who were about 60 years of age. They published their research in the journal eLife.

The scientists identified five common genetic changes that were most frequent in the 105+/110+ groups, between two genes known as COA1 and STK17A. Analysis showed the same variants in the people over 100. Computational analysis predicted these variations most likely modulated the expression of three different genes. The most common genetic changes were associated with increased activity of the STK17A gene in some tissues. This gene is known to be involved in coordinating cellular response to DNA damage, encouraging damaged cells to die via programmed cell death, and managing the amount of reactive oxygen species within a cell. The most common genetic changes were also associated to decreased activity of the COA1 gene in some tissues. This gene is involved in the correct crosstalk between the cell nucleus and mitochondria, the energy producers of the cells. This same region is also linked to an increased expression of BLVRA in some tissues, a gene important in eliminating reactive oxygen species.

“Previous studies showed that DNA repair is one of the mechanisms allowing an extended lifespan across species,” said Cristina Giuliani, senior assistant professor at the Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, University of Bologna, and senior author of the study. “We showed that this is true also within humans, and data suggest that the natural diversity in people reaching the last decades of life are, in part, linked to genetic variability that gives semi-supercentenarians the peculiar capability of efficiently managing cellular damage during their life course.”

Most Comprehensive Study to Date of COVID-19 Hospital Mortality

Investigators at the University of Washington conducted what is so far the most comprehensive evaluation of changes in hospital mortality for COVID-19. They analyzed data from more than 20,000 patients admitted for COVID-19 from March 2020 to November 2020. They found that in-hospital mortality in this patient population dropped 38% between March and May, but there was not much more drop through November 2020. The goal was to discover the most likely cause of the trends by controlling for patient age, sex, comorbidities, and severity of disease when the patient was admitted. None of those factors, however, fully explained the drop. They suspect the drop in mortality might be due to overloaded hospitals and changes in treatment.

Open-Source Online Suite of Computational Models to Screen for Drugs for COVID-19

Scientists at the University of New Mexico Health Sciences Center developed an open-source online suite of computational models that allows researchers to quickly screen small molecules for possible COVID-19-fighting properties. Called REDIAL-2020, they built it on data from their own COVID drug repurposing studies after realizing there was enough data to build solid machine learning models from it. The assays gauged each molecule’s ability to inhibitor viral entry, infectivity and reproduction, and its ability to protect a cell from being killed by the virus.

Specific IgG Antibody Identified in Crohn’s Disease Patients

Researchers at the University of Alabama at Birmingham described IgG antibodies in Crohn’s disease patients that are specific for human-derived flagellins of bacteria in the Lachnospiraceae family.  Crohn’s disease and ulcerative colitis are inflammatory bowel diseases marked by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals. Flagellins are the building blocks of the hairlike motility flagella that are attached to the bacterial cell wall. Flagellin is a potent immune activator and antigen. It is also the only microbial protein known to have three receptors for innate immunity encoded in the host genome, as well as immunoglobulin and T-cell receptors. The Crohn’s patients in the study, but not the ulcerative colitis patients, had augmented serum IgG antibodies to Lachnospiraceae flagellins from various species of Roseburia and one species of Eubacterium, which are normal flora in the human small intestine, specifically the third segment of the small intestine.

An Even Better Gene Editing System than CRISPR?

CRISPR is a revolutionary and simple way to perform gene edits. And in the decade it’s been in existence, researchers have found ways to improve on it. Now, investigators with the Wyss Institute for Biologically Inspired Engineering at Harvard have developed a new gene editing tool called Retron Library Recombineering (RLR). It has the ability to create up to millions of mutations simultaneously and “barcodes” mutant bacterial cells so the entire pool can be screened at the same time. They believe it can be used where CRISPR is either toxic or not feasible, and appears to have better editing rates.

One of the biggest limitations of CRISPR-Cas9 is that the same capability that finds and cuts specific DNA pieces tricks the cell into inserting a new piece of DNA to repair the break. This can be very complicated and may be toxic because the cuts at times occur at off-target sites, with possible unintended consequences. The researchers published their research in the journal PNAS.

“Being able to analyze pooled, barcoded mutant libraries with RLR enables millions of experiments to be performed simultaneously, allowing us to observe the effects of mutations across the genome, as well as how those mutations might interact with each other,” said senior author George Church, who leads the Wyss Institute’s Synthetic Biology Focus Areas and is also a professor of Genetics at HMS. “This work helps establish a road map toward using RLR in other genetic systems, which opens up many exciting possibilities for future genetic research.”