Resources

Single-cell transcriptomic profiling of young and old mouse brains following heterochronic parabiosis shows regulation of several canonical hallmarks of aging by a shift in age-induced changes of the transcriptome in a cell-type-specific manner.

By applying quantitative chemical cross-linking technologies, the authors show that changes in the mitochondrial interactome of the skeletal muscle contribute to mitochondrial functional decline in female mice.

Zhao et al. find evolutionarily conserved astrocyte and microglia subpopulations shared across multiple brain regions and reveal similarities and differences between AD and PD glia and regional variance linked to AD pathology and neurodegeneration.

Single-cell transcriptomic data from a neurogenic region of the mouse brain were used to build aging clocks for specific neural cell types. These clocks showed that heterochronic parabiosis and exercise lead to distinct transcriptomic rejuvenation patterns across cell types.

This study identifies CSF proteins specifically dysregulated along the AD continuum that reflect the multifactorial nature of disease progression. Some of these CSF proteins were used to build biomarker panels with high diagnostic accuracies.

The hypothalamus controls homeostatic functions such as metabolism and sleep, which undergo age-related changes. Here the authors perform single-nuclei transcriptomics profiling of young and old hypothalamus from female mice and describe changes in gene expression with age, in particular increased expression of the X inactivation gene Xist.

Luo et al. report a single-cell landscape of human blood from newborn to frailty. Comprehensive profiling uncovers frailty-specific immune cells and gene expression signatures useful for formulating a clinically relevant screen for unhealthy aging.

The authors find extensive remodeling of the gut microbiome and blood metabolome in extremely long-lived individuals (94–105 years old) compared to their children (50–79 years old) and report distinct generation-specific and cross-generational associations with genetic and socioeconomic factors.

The authors measured blood cell telomere length in 474,074 participants of UK Biobank providing a major resource for assessing the role of this proposed marker of biological age in human health and disease.

With aging, the immune system undergoes severe changes that impact health in numerous ways. For a comprehensive, translational analysis of these alterations, Krishnarajah et al. here provide profiling of immune cell populations across 12 tissues from young and old mice.

As part of Myeloid Cells in Neurodegenerative Disease (MyND) initiative, the authors profiled the transcriptome of primary monocytes and microglia from patients with Parkinson’s disease and controls, revealing the pathways and genes that are altered in the immune system of patients with Parkinson’s disease.

The authors report whole-blood RNA-seq for 4,871 samples from 1,570 participants in the Parkinson Progression Marker Initiative. This Resource documents blood-based transcriptomic changes associated with PD, including early increases in neutrophil gene expression with a decrease in lymphocytes.

Lu and colleagues generated a transcriptomic, lipidomic and metabolomic atlas of primary bone-marrow mouse neutrophils with organismal aging and across biological sexes, revealing lifelong sex-dimorphic neutrophil functional regulation.

Morshed et al. analyzed the proteome and phosphoproteome of brain tissue from patients with Alzheimer’s disease. The analysis of patient heterogeneity links glia pathologies and signaling pathways to stages of disease progression.

Walker et al. report a proteome-wide association study that identifies 38 candidate proteins in nondemented older adults that are associated with future dementia risk. Pathway analysis of these proteins implicates immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.

Arthur et al. report the biochemical and proteomic (SomaLogic) profiling of plasma and CyTOF immunophenotyping of peripheral blood mononuclear cells from 71 individuals with COVID-19 or other inflammatory pulmonary diseases, and 148 healthy donors aged 25–80 years old. The Resource reveals unique determinants of COVID-19 disease relative to healthy aging and other pulmonary disorders.

The authors present a small noncoding RNA atlas characterizing two longitudinal Parkinson’s disease cohorts and reveal potential biomarkers for disease detection, their relation to molecular hallmarks of PD and regulatory disease-progression modules.

Multiomics profiling of circulating monocytes from young and older healthy males reveals key determinants of healthy aging, including regions of age-associated DNA hypo- and hypermethylation, cellular chromatin landscape and effect on gene expression.