GeroScience最新文献

Background: Intervertebral disc degeneration (IVDD) is a leading contributor to lower back pain, yet its underlying mechanisms remain poorly defined. While insulin-like growth factor 1 (IGF-1) has been implicated in disc homeostasis, the specific contributions of growth hormone (GH)-a key upstream regulator of IGF-1 that also acts and independently influences skeletal tissues-have not been thoroughly investigated in the context of IVDD.

Methods: We utilized transgenic mouse models with altered GH signaling, including bovine GH (bGH)-expressing and GH receptor antagonist (GHA) mice, to investigate how GH excess or GH antagonism influences disc structure, degeneration, and to identify potential molecular pathways involved in disc maintenance and degradation. Disc histology was evaluated using Safranin-O/Fast Green staining and quantitative scoring across the nucleus pulposus (NP), annulus fibrosus (AF), and endplate (EP) compartments. Bulk RNA sequencing was conducted on intervertebral discs harvested from 12-month-old bovine GH-overexpressing (bGH) and wild-type (WT) mice to identify transcriptional changes associated with GH overexpression.

Results: bGH mice developed visible IVDD as early as 3 months of age, with degenerative features across all disc compartments. At 15 months, bGH males exhibited more severe degeneration than females, including greater proteoglycan loss, disc height reduction, and fibrotic remodeling. In contrast, 2-year-old GHA mice were protected from age-related disc degeneration, maintaining disc integrity and low histological scores. Transcriptomic analysis revealed sex-specific upregulation of inflammatory and catabolic pathways in bGH discs, including TNF, IL-17, and NOD-like receptor signaling, alongside downregulation of anabolic and ECM maintenance pathways such as PI3K-Akt and mTOR. Notably, these effects were more pronounced in males than females.

Conclusion: Abundance of GH accelerates IVDD through sex-dependent activation of inflammatory and matrix-degrading pathways, while GH antagonism confers protection against age associated disc degeneration. These findings identify GH as a critical regulator of disc homeostasis and a potential therapeutic target for mitigating IVDD and associated low back pain.

Rapid eye movement sleep behavior disorder (RBD) is increasingly recognized as a significant clinical feature in neurodegenerative diseases like Alzheimer's disease (AD) and Lewy body dementia (LBD). This study investigates the prevalence and clinical implications of RBD among individuals diagnosed with AD and LBD, emphasizing its relationship with cognitive decline. A retrospective observational study analyzed data from 5,481 participants across four diagnostic groups: AD + LBD, AD, LBD, and cognitively normal controls. Multinomial logistic regression and multivariable analyses were performed to assess RBD associations with demographic, clinical, and neuropsychiatric factors. Limitations include reliance on self-reported questionnaires to identify RBD, which may lead to underdiagnosis and skewed prevalence estimates. RBD prevalence was significantly higher in the AD + LBD (37.40%) and LBD (69.30%) groups compared to AD (3.61%) and cognitively normal controls (2.31%). The odds ratio (OR) for RBD in the AD + LBD group was 12.39 compared to controls (p < 0.001). Other significant associations included male gender and higher neuropsychiatric symptom severity, while age and education demonstrated complex relationships with RBD prevalence. This study highlights RBD as a critical factor in neurodegenerative disease assessment and an early marker for identifying at-risk individuals. Recognizing RBD's role in cognitive decline emphasizes the need for integrated clinical approaches that incorporate sleep assessments in dementia management and inform strategies for improving patient quality of life.

Aging humans and non-human primates both exhibit a similar pattern of cognitive decline beginning in middle age that is characterized by progressive impairments in rule learning, executive function, and working and recognition memory-functions often associated with dysfunction of prefrontal and medial temporal lobe regions. The heterogeneity and inter-subject variability in aging and age-related cognitive impairments present challenges for developing effective therapeutics and can be attributed to differing degrees of cortical white matter (WM) damage and alterations to local and long-range prefrontal and temporal networks. A promising therapeutic that has been shown to be efficacious in mitigating WM damage and improving cognitive function in rodent models is mesenchymal cell-derived extracellular vesicles (MSC-EVs). In the present study, late middle-aged rhesus monkeys were systemically administered monkey-derived MSC-EVs every 2 weeks for 18 months. We demonstrate that MSC-EV treatment improves spatial working memory and decreases the frequency of perseverative responses with largely no effects on recognition memory. These cognitive improvements were associated with increases in MRI diffusion measures of WM structural integrity over time as well as preservation of inter-network functional connectivity as measured by resting-state functional MRI. These findings suggest that MSC-EV treatment can slow or reverse age-related cognitive decline while strengthening WM integrity and improving functional connectivity in late middle-aged rhesus monkeys.

In an era marked by a rapidly aging global population, delving into the intricate neurophysiological changes that accompany the aging process assumes paramount importance. This narrative review offers a comprehensive exploration of the intricate relationship between electromagnetic neuromodulation and electroencephalography (EEG) within the context of aging. Moreover, it showed the promising landscape of non-invasive neuromodulation techniques, encompassing established methodologies like transcranial magnetic stimulation (TMS) and transcranial direct and alternating current stimulation (tDCS/tACS). These modalities are analyzed for their potential to shape EEG marks in the aging population. These associations not only could broaden our understanding of the aging brain but could also suggest exciting scenarios for therapeutic interventions and cognitive enhancement among the elderly. Consequently, the comprehension of these mechanisms emerges as a critical key player for the development of precisely tailored interventions, aimed at mitigating age-associated cognitive decline and supporting robust brain health in the elderly.

Gait alterations are recognized as early markers of age-related decline and cognitive impairment. Dual-task assessments, which impose cognitive load while walking, provide valuable insights into gait control limitations and cognitive-motor interactions in aging populations. This study evaluates age-related and cognitive load-induced changes in gait parameters, with a particular focus on asymmetry, and aims to optimize the gait assessment protocol for the Semmelweis Study framework. The Semmelweis Study is a large-scale workplace cohort investigating the determinants of unhealthy aging and promoting healthy brain aging by identifying risk factors and protective mechanisms influencing vascular, metabolic, and neurocognitive decline. As part of this initiative, gait analysis is emerging as a critical tool for assessing functional aging, detecting early signs of mobility and cognitive impairment, and contributing to biological age assessment. A cross-sectional analysis was conducted on adults aged 23 to 87 years using a pressure-sensitive walkway system. Participants were evaluated under single-task conditions (normal walking) and dual-task conditions (walking while performing a concurrent cognitive task). Spatiotemporal gait parameters, asymmetry indices, and dual-task costs were analyzed to assess age-related changes in gait performance and cognitive-motor interactions. Aging was associated with significant reductions in gait speed, step length, and stride length, along with a corresponding increase in gait asymmetry. Dual-task conditions exacerbated these alterations, indicating age-related impairments in cognitive-motor integration. Asymmetry indices were sensitive to aging effects, suggesting their potential as biomarkers for functional decline. The dual-task cost on gait was significantly greater in older adults, reinforcing the interplay between cognitive and motor systems in aging. Age-related gait alterations, particularly under cognitive load, underscore the importance of comprehensive gait assessments in aging research. Our findings contribute to the optimization of the Semmelweis Study gait assessment protocol by identifying key gait parameters that capture functional decline and biological aging. Integrating dual-task gait analysis into large-scale epidemiological studies has the potential to enhance early detection of brain health decline, refine biological age estimation, and guide targeted interventions to support healthy aging and neuromotor resilience.