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Aging is characterized by a coordinated functional decline across multiple organs. While cell-autonomous mechanisms contribute to local aging phenotypes, the systemic synchronicity of aging suggests a major role for cell non-autonomous drivers. Emerging evidence implicates the hypothalamus-a central regulator of neuroendocrine and homeostatic functions-as a potential source of circulating pro-geronic signals. A hallmark of brain aging is the accumulation of senescent cells, particularly in...

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Sleep alterations have long been associated with Alzheimer's disease (AD), but whether it is an early symptom or only develops later in the pathological progression remains unknown. To study this, 5xFAD heterozygous (Het) mice, a transgenic model of amyloid overexpression, and wild-type (WT) littermates at 1, 2, 3, 4 and 6 months of age were assessed within instrumented home cages to noninvasively score 3-state sleep using respirations and gross body movements during the dark cycle. Progressive...

BackgroundPsychological disorders and cognitive impairment frequently co-occur in older adults, posing challenges to healthy aging. This study aimed to examine the association between late-life psychological disorders and the risk of developing cognitive impairment.MethodsProspective study analyzed data from 28,706 older adults enrolled in the Taipei City Older Adults Health Examination (2012-2016), among whom 10.3% developed cognitive impairment during follow-up. Psychological disorders were...

Population aging is accelerating, yet the multi-organ aging process and the geroprotective effects of dietary protein restriction (PR) remain poorly understood. Here, we conducted comprehensive proteomic analyses on 41 mouse tissues during male mouse aging and PR. Our findings identified tissue-specific aging hallmarks, including widespread changes in immunoglobulins and serine protease inhibitors across multiple tissues. PR mitigated age-related tissue-specific protein expression, epigenomic...

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Cross-education (CE), the phenomenon whereby unilateral strength training induces neuromuscular adaptations in the contralateral limb, is underpinned by distributed cortical and subcortical plasticity. This study evaluated acute neural responses to a single bout of metronome-paced unilateral strength training in younger (n = 17; 27 ± 6 years) and older adults (n = 18; 67 ± 5 years). Neurophysiological assessments included corticospinal excitability and inhibition via transcranial magnetic...

Ending Palmer lease is one of many belt-tightening moves amid budget uncertainty

The "eye-brain axis" refers to the dynamic system of interactions between the eyes and the brain, collectively encompassing the visual signal transmission and integration pathways. The eyes and the brain exhibit structural and functional synergy, and visual dysfunction not only impairs information processing within the eye but also induces structural and functional remodeling of the central nervous system (CNS) via the eye-brain axis. For instance, the effects of glaucoma on the visual cortex...

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily marked by the degeneration of dopaminergic neurons and pathological α-synuclein (α-syn) accumulation. Although insulin-degrading enzyme (IDE) has been implicated in both type 2 diabetes mellitus and amyloid-protein clearance, its precise relevance to PD pathogenesis remains unclear. In this study, we show that IDE expression is reduced in the nigrostriatal region of aging homozygous A53T α-syn mice and in...

ObjectiveThis study evaluated the effectiveness of a novel multidimensional group intervention aimed at enhancing subjective cognitive and psychosocial functioning in community-dwelling older adults.MethodsSixty cognitively healthy adults aged 65-75 were randomly assigned to an experimental or control group. The 10-week intervention integrated five components: memory compensation, problem solving, emotion regulation, mindfulness, and locus of control. Validated self-report measures were...

Aging is a multifaceted process involving cellular senescence and a significant remodeling of the immune network driven by the senescence-associated secretory phenotype (SASP). This progressive process needs adaptable drivers to push it forward. The redox-sensitive high mobility group box 1 (HMGB1) protein is a perfect example of this kind of oxidative stress- and aging-related multifunctional protein. The HMGB1 protein is an important non-histone DNA chaperone which maintains chromatin...

Cellular senescence is a state where cells permanently exit the cell cycle after a finite number of divisions, while maintaining metabolic activity. This phenomenon, initially described by Leonard Hayflick, plays a pivotal role in aging, contributing to the progressive decline in physiological function by promoting tissue dysfunction and restricting regenerative capacity. It is regulated by an array of factors, including DNA damage, telomere shortening, oxidative stress, mitochondrial...

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily marked by the degeneration of dopaminergic neurons and pathological α-synuclein (α-syn) accumulation. Although insulin-degrading enzyme (IDE) has been implicated in both type 2 diabetes mellitus and amyloid-protein clearance, its precise relevance to PD pathogenesis remains unclear. In this study, we show that IDE expression is reduced in the nigrostriatal region of aging homozygous A53T α-syn mice and in...

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a...

Age-related thymic involution increases vulnerability to cancers and infection in older adults, yet the driving mechanisms and its impact on peripheral T cells remain unclear. Using single-cell sequencing, we here analyzed 387,762 cells from human thymus and peripheral blood of young and aged individuals. Within thymus, we found aging reduced T-lineage potential in early thymic progenitors but increased innate lymphocyte lineage potential. Aged thymus were enriched in mature T cells with low...

CONCLUSIONS: Older age, gender, and chronic diseases play pivotal roles in frailty transitions, with heart disease identified as an important factor for frailty improvement in both genders. Early frailty screening and sex-sensitive approaches may help mitigate frailty progression among community-dwelling older adults.

Golgi fragmentation is an early and common feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). However, whether a shared mechanism drives Golgi fragmentation across different neurodegenerative conditions remains unclear. Here, we identify the E3 ubiquitin-protein ligase Itchy homolog (ITCH) as a key regulator of proteotoxicity through its role in inducing Golgi fragmentation. Disease-associated accumulation of ITCH promotes...

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With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension (D(f)) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of D(f) on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1. We...