Longevity Papers

Musical training can counteract age-related decline in speech perception in noisy environments. However, it remains unclear whether older non-musicians and musicians rely on functional compensation or functional preservation to counteract the adverse effects of aging. This study utilized resting-state functional connectivity (FC) to investigate functional lateralization, a fundamental organization feature, in older musicians (OM), older non-musicians (ONM), and young non-musicians (YNM). Results showed that OM outperformed ONM and achieved comparable performance to YNM in speech-in-noise and speech-in-speech tasks. ONM exhibited reduced lateralization than YNM in lateralization index (LI) of intrahemispheric FC (LI_intra) in the cingulo-opercular network (CON) and LI of interhemispheric heterotopic FC (LI_he) in the language network (LAN). Conversely, OM showed higher neural alignment to YNM (i.e., a more similar lateralization pattern) compared to ONM in CON, LAN, frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN), indicating preservation of youth-like lateralization patterns due to musical experience. Furthermore, in ONM, stronger left-lateralized and lower alignment-to-young of LI_intra in the somatomotor network (SMN) and DAN and LI_he in DMN correlated with better speech performance, indicating a functional compensation mechanism. In contrast, stronger right-lateralized LI_intra in FPN and DAN and higher alignment-to-young of LI_he in LAN correlated with better performance in OM, suggesting a functional preservation mechanism. These findings highlight the differential roles of functional preservation and compensation of lateralization in speech perception in noise among elderly individuals with and without musical expertise, offering insights into successful aging theories from the lens of functional lateralization and speech perception.

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood-brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.