Aggregator

Lysosomes maintain a highly acidic lumen to regulate H^(+)-dependent hydrolase-mediated degradation, but how protons are 'leaked' out to regulate organellar functions through cytosolic effectors remains unknown. Here we developed DNA nanodevices on the cytosolic leaflet of lysosomal membranes to monitor juxta-organellar pH in cells. Unexpectedly, we revealed a radiating acidic layer (up to 21 nm in thickness) on the outer surface of all lysosomes, typically 0.2-0.7 pH units more acidic than the...

Physical activity (PA) is associated with lower dementia risk, yet few studies examine objectively measured PA with concurrently measured brain and cognitive aging outcomes longitudinally, leaving a gap in knowledge regarding temporality of these brain-behavior associations. We examined how longitudinal within-person changes in average daily step count track with changes in memory, executive function, hippocampal volumes, white matter hyperintensities (WMH), and depressive symptoms over time....

The long-term body mass index (BMI) threshold to prevent mortality among aging individuals with type 2 diabetes mellitus (T2DM) remains unclear. We quantify BMI exposure using two metrics: the percentage of time BMI above target range (TAR) and the percentage of time BMI within target range (TTR). In a cohort of 3,708 adults aged ≥40 years with T2DM and at least 5 BMI measurements across 4 years, 1,020 deaths occurred during a median 5-year follow-up. Sustained BMI ≥27 kg/m² (TAR) is positively...

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, which represents the most prevalent dementia worldwide. Although amyloid-β (Aβ) and tau pathology have been the classic focus of treatment, accumulating evidence indicates that ageing-associated cellular senescence plays a central role in AD pathogenesis. Senescent neurons, astrocytes, microglia and endothelial cells accumulate in the ageing and Alzheimer's brain and adopt a senescence-associated secretory...

No abstract

Aging increases breast cancer risk while an early first pregnancy reduces a woman's life-long risk. Several studies have explored the effect of either aging or pregnancy on mammary stem/progenitor cells, however, the combined effect of both remains unclear. Here, we interrogate the functional and transcriptomic changes at single-cell resolution in the mammary gland of aged nulliparous and parous mice to discover that pregnancy normalizes age-related imbalances in lineage composition, while also...

Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in heterogeneous systems. However, this technique often results in the reanalysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we develop PIP-seq for Rare-cell Enrichment and Sequencing (PURE-seq). PURE-seq allows direct FACS sorting of cells into PIP-seq reactions, minimizing handling and reducing cell loss. PURE-seq reliably sequences...

The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis^(1,2). Although abnormal crossover recombination is known to confer risk for aneuploidy^(3,4), limited data have hindered understanding of the potential shared genetic basis of these key molecular phenotypes. To address this gap, we performed retrospective analysis of pre-implantation genetic testing data from 139,416 in vitro fertilized embryos from 22,850 sets of...

Neurodegenerative diseases affect 1 in 12 people globally and remain incurable. Central to their pathogenesis is a loss of neuronal protein maintenance and the accumulation of protein aggregates with ageing^(1,2). Here we engineered bioorthogonal tools³ that enabled us to tag the nascent neuronal proteome and study its turnover with ageing, its propensity to aggregate and its interaction with microglia. We show that neuronal protein half-life approximately doubles on average between 4-month-old...

No abstract

No abstract

No abstract

Mitochondrial dysfunction is recognized as a biological hallmark of aging; however, bioenergetic capacity across the healthy human life course remains insufficiently characterized. While aging is generally associated with a systemic decline in mitochondrial function ("age-related bioenergetic decline"), recent research suggests that age-related bioenergetic differences are context dependent. Blood cells are extensively utilized as accessible samples for human bioenergetic profiling; therefore,...

CONCLUSION: Different sleep duration trajectories are associated with the risk of cognitive impairment, indicating that monitoring dynamic changes in sleep patterns may provide early warning value for cognitive health in the elderly.

CONCLUSION: The findings revealed that cerebrovascular accidents, knee osteoarthritis, and lumbar spondylosis are key contributors to disability in geriatric outpatients. Addressing these conditions can help tailor physiotherapy to improve older adults' functional independence and quality of life.

Neuro- and retinal degenerative diseases, including Alzheimer's, stroke, age-related macular degeneration, and central retinal artery occlusion, rob millions of their independence. Studying these diseases in human retinas has been hindered by the rapid loss of neuronal activity after death. While some CNS activity has been restored postmortem, synchronized neuronal transmission beyond 30 min has remained elusive. We overcome this barrier by reviving and sustaining light signal transmission in...

CONCLUSION: CS maintained better exercise performance in older adults, accompanied by perception that they could perform more repetitions compared to TRAD. However, the CS implemented did not significantly reduce perceived exertion.

Aging is associated with profound alterations in immune cell composition and function, yet the impact on peripheral γ/δ T-cell subsets remains incompletely understood. Here, we show that the peripheral γ/δ T-cell compartment is markedly remodeled with age in mice. Specifically, innate-like Ly-6C^(-) CD44^(hi) γ/δ T cells expand in secondary lymphoid organs (SLOs) of aged mice, while adaptive-like subsets decline. This age-related shift is accompanied by enhanced functionality, with Ly-6C^(-)...

CONCLUSION: Our findings highlight HRV's dynamic nature and the need to consider the time of day when investigating the relationship between HRV and cognition. Compared to daytime HRV, reduced nighttime HRV may have a stronger association with worse cognition.