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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...

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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.