Aging & Longevity

Structural features within the NORAD long noncoding RNA underlie efficient repression of Pumilio activity

2 months 1 week ago
Long noncoding RNAs (lncRNAs) are increasingly appreciated for their important functions in mammalian cells. However, how their functional capacities are encoded in their sequences and manifested in their structures remains largely unknown. Some lncRNAs bind to and modulate the availability of RNA-binding proteins, but the structural principles that underlie this mode of regulation are unknown. The NORAD lncRNA is a known decoy for Pumilio proteins, which modulate the translation and stability...
Svetlana Farberov

Proteomic analysis across aged tissues reveals distinct signatures and the crucial involvement of midgut barrier function in the regulation of aging

2 months 1 week ago
The process of aging is a natural phenomenon characterized by gradual deterioration in biological functions and systemic homeostasis, which can be modulated by both genetic and environmental factors. Numerous investigations conducted on model organisms, including nematodes, flies, and mice, have elucidated several pivotal aging pathways, such as insulin signaling and AMPK signaling. However, it remains uncertain whether the regulation of the aging process is uniform or diverse across different...
Congying Zhang

A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring

2 months 1 week ago
Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 96 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in...
Todd W Dowrey

Proteins required for stereocilia elongation during mammalian hair cell development ensure precise and steady heights during adult life

2 months 1 week ago
The hair bundle, or stereocilia bundle, is the mechanosensory compartment of hair cells (HCs) in the inner ear. To date, most mechanistic studies have focused on stereocilia bundle morphogenesis, and it remains unclear how this organelle critical for hearing preserves its precise dimensions during life in mammals. The GPSM2-GNAI complex occupies the distal tip of stereocilia in the tallest row and is required for their elongation during development. Here, we ablate GPSM2-GNAI in adult mouse HCs...
Elli I Hartig

Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling

2 months 1 week ago
Central tolerance of thymocytes to self-antigen depends on the medullary thymic epithelial cell (mTEC) transcription factor autoimmune regulator (Aire), which drives tissue-restricted antigen (TRA) gene expression. Vitamin D signaling regulates Aire and TRA expression in mTECs, providing a basis for links between vitamin D deficiency and autoimmunity. We find that mice lacking Cyp27b1, which cannot produce hormonally active vitamin D, display profoundly reduced thymic cellularity, with a reduced...
Patricio Artusa

Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling

2 months 1 week ago
Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38^(hi) expression universally identified CD8^(+) and CD4^(+) RTEs. We further...
Pavla Bohacova

Advances in Human Cellular Mechanistic Understanding and Drug Discovery of Brain Organoids for Neurodegenerative Diseases

2 months 1 week ago
The prevalence of neurodegenerative diseases (NDs) is increasing rapidly as the aging population accelerates, and there are still no treatments to halt or reverse the progression of these diseases. While traditional 2D cultures and animal models fail to translate into effective therapies benefit patients, 3D cultured human brain organoids (hBOs) facilitate the use of non-invasive methods to capture patient data. The purpose of this study was to review the research and application of hBO in...
Tong Lei

Impact of age and sex on heart rate variability and cardiometabolic function in healthy adults

2 months 1 week ago
Heart rate variability (HRV) is a non-invasive measure of cardiac autonomic function. A clearer understanding as to whether resting autonomic function represented by HRV could be associated with changes in peak exercise cardiac function remains unanswered. This study evaluated the effect of age and sex on HRV, cardiometabolic function, and determined the correlation between HRV and cardiac function in healthy individuals. Sixty-eight participants (age range: 19-78 years old, females, n = 28)...
Alaa I Alyahya

Interplay of education and DNA methylation age on cognitive impairment: insights from the Health and Retirement Study

2 months 1 week ago
Few studies have assessed the association of educational attainment on dementia and cognitive impairment through DNA methylation age acceleration, while accommodating exposure-mediator interaction effects. We evaluated the mediation role of six epigenetic clocks with dementia, cognitive impairment non-dementia, and normal cognition, while accommodating exposure-mediator interaction effects. To understand the joint association of low education (≤12 years) and DNA methylation age acceleration...
Erin B Ware

Co-residence with children as a mediator between widowhood and loneliness in older adults

2 months 1 week ago
CONCLUSION: Alterations in living arrangements play a pivotal role in mediating the effects of widowhood on loneliness among China's older adults. Encouraging co-residence with adult children post-spousal loss, especially for older women and the eldest age groups, might mitigate social isolation. These insights both deepen our theoretical understanding and suggest interventions to enhance the well-being of widowed older adults.
Kaishan Jiao

Decisional needs for older adults, home health care nurses and dental hygienists during team-based oral health assessments in ordinary home settings - a qualitative study

2 months 1 week ago
CONCLUSION: It is important for key participants in ordinary home settings to participate in interprofessional teams in home health care. To further anchor this in theory, conceptual models for professionals from different care organizations (municipal care, dental care) need to be developed that also involve older adults as participants. Future research could bridge theory and practice by including theories of learning while exploring interorganizational oral health planning in home settings.
Jessica Persson Kylén

The resistance of domestic canine skin-derived fibroblasts to oxidative and non-oxidative chemical injury: implications of breed and body size

2 months 1 week ago
Small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. Underlying this observed physiological difference across domestic dogs, there must also be differences at other levels of organization that could lead to elucidating what accounts for the disparity in aging rates and life span within this species. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated....
James M Harper

Development, characterization, and replication of proteomic aging clocks: Analysis of 2 population-based cohorts

2 months 1 week ago
CONCLUSIONS: In this longitudinal study, we found that the ARIC PACs and published PACs were similarly associated with an increased risk of mortality. These findings suggested that PACs show promise as biomarkers of biological age. PACs may be serve as tools to predict mortality and evaluate the effect of anti-aging lifestyle and therapeutic interventions.
Shuo Wang

ProNGF elicits retrograde axonal degeneration of basal forebrain neurons through p75<sup>NTR</sup> and induction of amyloid precursor protein

2 months 1 week ago
Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75^(NTR). Here, we investigated the signaling cascades initiated at the axon...
Srestha Dasgupta
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