Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity.

Background: Age-related changes in immune cell composition and functionality are associated with multimorbidity and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite immunity that remains highly functional at extreme old age.

Methods: To identify immune-specific patterns of aging and extreme human longevity, we analyzed novel single cell profiles from the peripheral blood mononuclear cells (PBMCs) of a random sample of 7 centenarians (mean age 106) and publicly available single cell RNA-sequencing (scRNA-seq) datasets that included an additional 7 centenarians as well as 52 people at younger ages (20-89 years).

Bayesian Differential Analysis of Cell Type Proportions.

The analysis of cell type proportions in a biological sample should account for the compositional nature of the data but most analyses ignore this characteristic with the risk of producing misleading conclusions. The recent method scCODA appropriately incorporates these constraints by using a Bayesian Multinomial-Dirichlet model that requires a reference cell type to normalize the distribution of all cell types. However, a reference cell type that is stable across biological conditions may not always be available.

A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants.

We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609, = 7.

Cell Type Diversity Statistic: An Entropy-Based Metric to Compare Overall Cell Type Composition Across Samples.

Changes of cell type composition across samples can carry biological significance and provide insight into disease and other conditions. Single cell transcriptomics has made it possible to study cell type composition at a fine resolution. Most single cell studies investigate compositional changes between samples for each cell type independently, not accounting for the fixed number of cells per sample in sequencing data.

Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program.

Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide.