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Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Here, we report a whole genome, multiparametric CRISPR screen, identifying 43 genes that can rescue multiple cellular phenotypes associated with progeria. We implement the screen in fibroblasts from Néstor-Guillermo Progeria Syndrome male patients, carrying a homozygous A12T mutation in BAF. The hits are enriched for genes involved in protein synthesis, protein and RNA transport and...

The dysfunction of the dopaminergic projection from the ventral tegmental area (VTA) to the medial prefrontal cortex (mPFC) is believed to play a key role in the pathophysiology of Parkinson's disease (PD) accompanied by executive dysfunction (EDF). In this study, we identified an abnormal increase in lysophosphatidylcholine (LPC) levels in PD patients, which closely correlates with the severity of cognitive impairment. LPC disrupts the miR-2885/TDP-43 signaling pathway in microglia, driving...

Visual function deteriorates throughout the natural course of aging. Age-related structural and functional adaptations are observed in the retina, the light-sensitive neuronal tissue of the eye where visual perception begins. Molecular mechanisms underlying retinal aging are still poorly understood, highlighting the need to identify biomarkers for better prognosis and alleviation of aging-associated vision impairment. Here, we investigate dynamics of transcriptional dysregulation in the retina...

Ageing is an inevitable biological process that impacts the immune system, leading to immunosenescence and inflammaging, which contribute to increased susceptibility to infections, autoimmune diseases and cancers in individuals over the age of 65. This review focuses on the ageing of lymph node stromal cells (LNSCs), which are crucial for maintaining lymph node (LN) structure and function. Age-related changes in LNs, such as fibrosis and lipomatosis, disrupt the LN architecture and reduce immune...

Age-related cognitive decline varies widely among individuals, with some showing resilience despite older age. This study examines synaptic markers of glutamatergic and GABAergic neurotransmission in the hippocampus and cortex of older rats with differing cognitive abilities, aiming to uncover mechanisms that contribute to cognitive resilience. We observed significant age-related reductions in vesicular glutamate transporter VGluT1, particularly in the stratum oriens (SO), radiatum (SR), and...

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that produces the secondary messenger cGAMP. cGAMP activates the endoplasmic reticulum-associated adaptor stimulator of interferon genes (STING) and activates the innate immune system to produce a type I interferon response. Besides sensing microbial DNA, cGAS can also be activated by self-DNA or endogenous DNA, including that derived from genotoxic extranuclear chromatin and...

Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identify markers for...

CONCLUSION: The findings of this study revealed the potential influence of nutritional status on QoL, in enhancing QoL outcomes.

Inspiring Undergraduate Student Training in Alzheimer's Research (USTAR) aims to provide Underrepresented Minority (URM) undergraduate students with mentored didactic, clinical, and research experiences to stimulate interest in research related to Alzheimer's Disease and Related Dementias (ADRD). USTAR specifically focuses on social determinants of health (SDOH) as risk factors for ADRD minoritized populations. USTAR's scientific rationale is that URM undergraduates are less likely to enter the...

Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson's disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous...

Aging is an extremely significant risk associated with neurodegeneration. The most prevalent neurodegenerative disorders (NDs), such as Alzheimer's disease (AD) are distinguished by the prevalence of proteinopathy, aberrant glial cell activation, oxidative stress, neuroinflammation, defective autophagy, cellular senescence, mitochondrial dysfunction, epigenetic changes, neurogenesis suppression, increased blood-brain barrier permeability, and intestinal dysbiosis that is excessive for the...

No abstract

While the intestinal epithelium has the highest cellular turnover rates in the mammalian body, it is also considered one of the tissues most resilient to aging-related disorders. Here, we reveal an innate protective mechanism that safeguards intestinal stem cells (ISCs) from environmental conditions in the aged intestine. Using in vivo phenotypic analysis, transcriptomics, and in vitro intestinal organoid studies, we show that age-dependent activation of interferon-γ (IFN-γ) signaling and...

The study of biomarkers in biofluids and tissues expanded our understanding of the biological processes that drive physiological and functional manifestations of aging. However, most of these studies were limited to examining one biological compartment, an approach that fails to recognize that aging pervasively affects the whole body. The simultaneous modeling of hundreds of metabolites and proteins across multiple compartments may provide a more detailed picture of healthy aging and point to...

CONCLUSIONS AND IMPLICATIONS: Frailty is significantly associated with lower QoL in both middle-aged and older adults. In addition, the interaction of age and frailty showed that QoL improves with age in frail people. This suggests that the impact of frailty on QoL is greater in middle age.

Chronic loss of cardiomyocyte integrity underlies human heart failure associated with aging that often involves progression of acute myocardial infarction and the maladaptive response of cardiomyopathy. SW033291, an inhibitor of 15-prostaglandin dehydrogenase (15-PGDH), has been shown to mitigate fibrosis of mice heart. Whether it has cardioprotective effect remain unknown. Young and aged C57BL/6 J mice were treated with either the vehicle or SW033291 for four weeks. The expression of the target...

Aging is an extremely significant risk associated with neurodegeneration. The most prevalent neurodegenerative disorders (NDs), such as Alzheimer's disease (AD) are distinguished by the prevalence of proteinopathy, aberrant glial cell activation, oxidative stress, neuroinflammation, defective autophagy, cellular senescence, mitochondrial dysfunction, epigenetic changes, neurogenesis suppression, increased blood-brain barrier permeability, and intestinal dysbiosis that is excessive for the...

For the intricate and infrequent safety issues of batteries, online safety fault diagnosis over stochastic working conditions is indispensable. In this work, we employ deep learning methods to develop an online fault diagnosis network for lithium-ion batteries operating under unpredictable conditions. The network integrates battery model constraints and employs a framework designed to manage the evolution of stochastic systems, thereby enabling fault real-time determination. We evaluate the...

Inflammation is a significant driver of ischemic stroke pathology in the brain. To identify potential regulators of inflammation, we performed single-cell RNA sequencing (scRNA-seq) of young and aged mouse brains following stroke and found that interferon alpha-inducible protein 27 like 2 A (Ifi27l2a) was significantly up-regulated, particularly in microglia of aged brain. Ifi27l2a is induced by interferons for viral host defense and has been linked with pro-inflammatory cellular mechanisms....

CONCLUSION-DISCUSSION: The LASA-SBQ was translated into Turkish and culturally adapted. The psychometric properties of the questionnaire were examined and validity and reliability analyses were performed. The Turkish version of the LASA-SBQ is a valid and reliable scale and is suitable for use in scientific research.