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Microglia, the resident immune cells of the brain, are now recognized as being active participants in the onset and progression of many neurological and neuropsychiatric disorders. As a result, substantial effort has been made in finding ways to target, deplete or modulate the aberrant phenotypes of the microglia that are present in these different disease states, albeit with varied levels of success. The gut microbiota has recently emerged as a master regulator of microglia throughout the...

No abstract

Presbycusis, one of the most widespread disorders, is in part associated with the loss of temporal precision within the central auditory system. A contributor to the dysfunctional temporal precision during aging is the substantial downregulation of GABA in the central inferior colliculus (ICc), the hub of ascending and descending inputs of the auditory midbrain. However, how GABAergic inputs across the tonotopic axis of the ICc change with age has not been well explored. We sought to determine...

Ageing is the most important risk factor for many common human diseases, including cancer, diabetes, neurodegeneration and cardiovascular disease. Consequently, combating ageing itself has emerged as a rational strategy for addressing age-related multimorbidity. Over the past three decades, multiple genetic and pharmacologic interventions have led to substantial extension of lifespan and healthspan in model organisms. However, it is unclear whether these interventions target the causal...

The blood-brain barrier (BBB) restricts the passage of protein-rich fluids through tight junctions (TJs) formed between brain endothelial cells (BECs). BBB restrictiveness diminishes with aging, but the underlying mechanisms remain unclear. BECs establish physical contact with pericytes via N-cadherin homophilic adhesion. In cortex tissue from young and middle-aged patients, the age-related loss of vascular N-cadherin corresponds with the disruption of occludin TJs. Genetic deletion of...

Cancer therapy is limited by resistance to standard-of-care chemotherapeutic and/or by treatment-associated toxicity. Identifying molecular mechanisms that modulate cellular toxicity is crucial for enhancing treatment efficacy. We characterize CDADC1, a vertebrate-specific orphan enzyme, as an unprecedented eukaryotic dCTP deaminase. CDADC1 catalyzes the conversion of dCTP into dUTP. While bacteria use this activity to sustain proliferation, CDADC1 evolved independently and is not required for...

Skeletal muscle is a primary tissue of dysfunction during both aging and obesity. Recently, the coincidence of obesity and aging has gained attention due to the intersection of the obesity epidemic with an aging demographic. Both aging and obesity are associated with marked defects in skeletal muscle metabolic health. Despite these findings, we have a poor understanding of how obesity and aging may interact to impact skeletal muscle mass and metabolic health. Therefore, we investigated the...

The process of ageing is extremely variable in progression and phenotypic features including significant variations in disease milestones, such as cognitive impairment, frailty, or recurrent falls. Our aim was to analyze the influence of lifestyle factors on motor and cognitive performance in a longitudinal ageing study in older people on healthy ageing. We conducted a longitudinal analysis in a cohort of 744 older participants (mean 70 years) over an 8-year period. Cognitive performance was...

Science, Volume 388, Issue 6752, June 2025.

Science, Volume 388, Issue 6752, June 2025.

Science, Volume 388, Issue 6752, June 2025.

Science, Volume 388, Issue 6752, June 2025.

Science, Volume 388, Issue 6752, June 2025.

Science, Volume 388, Issue 6752, June 2025.

Science, Volume 388, Issue 6752, June 2025.