Aging is a factor associated with poor prognosis in glioblastoma (GBM). It is therefore important to understand the molecular features of aging contributing to GBM morbidity. is a long noncoding RNA (lncRNA) over expressed in GBM tumors shown to promote resistance to the chemotherapeutic temozolomide (TMZ), and tumor aggressiveness. How the expression of is regulated is not known, nor is it known if its expression is associated with aging. By analyzing transcriptional data obtained from natural and pathological aging brain, we found that the expression of is high in pathological and naturally aging brains. YY1 physically associates with the promoter of and we found that along with , is induced by TMZ. We found that the promoter is activated by TMZ, and by YY1 over expression. Using CRISPRi to deplete YY1, we found that YY1 promotes up regulation of and the activation of its promoter during TMZ treatment. In addition, we identified two putative YY1 binding sites within the promoter, and used mutagenesis to find that they are essential for TMZ mediated promoter activation. Together, our data positions YY1 as an important regulator, demonstrating that is expressed in the natural and pathological aging brain, including during neurodegeneration and cancer. Our findings advance our understanding of expression, bringing forth a new link between TMZ resistance and aging, both of which contribute to GBM morbidity.
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http://dx.doi.org/10.18632/aging.203182 | DOI Listing |
Geroscience
January 2025
Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary.
Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer's disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely recognized for its cardiovascular benefits and may also reduce the risk of cognitive decline and dementia.
View Article and Find Full Text PDFCancers (Basel)
December 2024
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Background: Immunosenescence is the aging of the immune system, which is closely related to the development and prognosis of lung cancer. Targeting immunosenescence is considered a promising therapeutic approach.
Methods: We defined an immunosenescence gene set (ISGS) and examined it across 33 TCGA tumor types and 29 GTEx normal tissues.
Cancers (Basel)
December 2024
Department of Neurological Surgery, Houston Methodist Neurological Institute, Houston Methodist Hospital, Houston, TX 77030, USA.
Radiation has been used to treat meningiomas since the mid-1970s. Traditionally, radiation was reserved for patients unfit for major surgery or those with surgically inaccessible tumors. With an increased quantity and quality of imaging, and an aging population, there has been a rise in incidentally diagnosed meningiomas with smaller tumors at diagnosis time.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, 00185 Rome, Italy.
Patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8-12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid-tau biomarkers in ADMCI patients.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute of Immunology, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.
Gliomas are the most common and lethal forms of malignant brain tumors. We attempted to identify the role of the aging-suppressor gene and Klotho protein in the immunopathogenesis of gliomas. We examined genetic variants by PCR-RFLP and measured serum Klotho levels using the ELISA method.
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