Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity is altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing […]

Background: Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light on cellular […]

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1–3. Cerebrospinal fluid (CSF) makes up the immediate environment […]

Cerebrospinal fluid (CSF) proteins and their structures have been implicated in aging and neurodegenerative diseases. In the present study, we used limited proteolysis–mass spectrometry (LiP–MS) to screen for new aging-associated […]

The human brain vasculature is of great medical importance: its dysfunction causes disability and death1, and the specialized structure it forms—the blood–brain barrier—impedes the treatment of nearly all brain disorders2,3. […]

The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their […]

Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration1. The cognitive benefits of physical exercise are tied to an increased plasticity […]

Alzheimer’s disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function1. However, little is known about the contribution of the adaptive immune response in Alzheimer’s disease2. Here, […]

Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we […]

Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms1–3. However, an unbiased understanding of the cellular and molecular processes that are affected […]

Neurofilament light chain (NfL) has emerged as a promising blood biomarker for the progression of various neurological diseases. NfL is a structural protein of nerve cells, and elevated NfL levels […]

Organismal aging is often characterized as a steady, monotonic decline of organ and tissue function. However, recent studies indicate spatial and temporal variations of aging rates across the lifespan. We […]

We previously identified 529 proteins that had been reported by multiple different studies to change their expression level with age in human plasma. In the present study, we measured the […]

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been […]

The vascular interface of the brain, known as the blood–brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1,2,3. Yet, recent studies have demonstrated […]

The development of clinical interventions that significantly improve human healthspan requires robust markers of biological age as well as thoughtful therapeutic targets. To promote these goals, we performed a systematic […]

A rapidly ageing population and a limited therapeutic toolbox urgently necessitate new approaches to treat neurodegenerative diseases. Brain ageing, the key risk factor for neurodegeneration, involves complex cellular and molecular […]

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a […]

Aging is a predominant risk factor for several chronic diseases that limit healthspan1. Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects […]

An aged circulatory environment can activate microglia, reduce neural precursor cell activity and impair cognition in mice. We hypothesized that brain endothelial cells (BECs) mediate at least some of these […]

Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, […]

Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets of microglia during different […]

Motivation Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations […]

Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a […]

Bioorthogonal tools enable cell-type-specific proteomics, a prerequisite to understanding biological processes in multicellular organisms. Here we report two engineered aminoacyl-tRNA synthetases for mammalian bioorthogonal labeling: a tyrosyl (ScTyrY43G) and a […]