559 results match your criteria: "National Institute on Aging - Intramural Research Program[Affiliation]"

LINC02257 regulates malignant phenotypes of colorectal cancer via interacting with miR-1273g-3p and YB1.

Cell Death Dis

December 2024

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea.

Colorectal cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) are involved in the progression of various types of cancer. In this study, we aimed to identify potential causal lncRNAs in CRC through comprehensive multilevel bioinformatics analyses, coupled with functional validation.

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Background: Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women.

Methods And Results: A total of 121 286 study-eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which 16 108 major CVD events were documented.

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Extracellular vesicles (EVs) are involved in cell-to-cell communication. Following uptake, EV cargo molecules, including DNA, RNA, lipids, and proteins, influence gene expression and molecular signaling in recipient cells. Although various studies have identified disease-specific EV molecules, further research into their biogenesis and secretion mechanisms is needed for clinical application.

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Alzheimer's Disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults.

Geroscience

November 2024

Laboratory of Epidemiology and Population Sciences, National Institute On Aging, NIA/NIH/IRP, NIH Biomedical Research Center, National Institute On Aging Intramural Research Program, 251 Bayview Blvd, Suite 100, Baltimore, MD, 21224, USA.

Alzheimer's Disease (AD) is a complex polygenic neurodegenerative disorder. Its genetic risk's relationship with all-cause dementia may be influenced by the plasma proteome. Up to 40,139 UK Biobank participants aged ≥ 50y at baseline assessment (2006-2010) were followed-up for ≤ 15 y for dementia incidence.

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Article Synopsis
  • - Mitochondria are crucial for brain function and their dysfunction is associated with age-related cognitive decline.
  • - A study using rats examined if the mitochondrial respiratory capacity changes with cognitive aging, focusing on the frontal cortex.
  • - Results showed no significant differences in mitochondrial oxygen consumption or ATP synthase activity between young and aged rats, indicating that mitochondrial function may not be a key factor in cognitive impairment related to aging.
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Longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults remain under-studied, especially across sex, race and levels of anxiety. We examined longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults, before and after stratifying by sex, race and anxiety level, using data from 1460 Healthy Aging in Neighborhoods of Diversity across the Lifespan Study (HANDLS) participants aged 30-64 y at v (2004-2009), followed across 3 visits up to 2017. In addition to LnHcy, we used group-based trajectory models predicting z-transformed likelihood of greater LnHcy with age (Hcy).

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  • Multiple sclerosis (MS) is an autoimmune disease linked to both genetic and environmental factors, involving the immune system and myelin changes associated with RNA, particularly circular RNAs (circRNAs).
  • A study analyzed circRNA expressions in peripheral blood mononuclear cells (PBMCs) from five newly diagnosed MS patients and five healthy controls, using a microarray to identify significant differences.
  • The research found 64 differentially expressed circRNAs, with 53 downregulated in MS patients, validated in a larger cohort, suggesting a specific circRNA as a potential biomarker for MS severity and progression.
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Mitochondrial dysfunction is linked to physical impairment and dementia. Mitochondrial DNA copy number (mtDNAcn) from blood may predict cognitive decline and dementia risk, but the effect of somatic mutations or frailty is unknown. We estimated mtDNAcn using fastMitoCalc and microheteroplasmies using mitoCaller, from Whole Genome Sequencing (WGS) data.

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Striving for clarity in language about gene expression.

Nucleic Acids Res

October 2024

Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.

What do we mean when we say 'gene expression'? In the decades following Crick's 1958 central dogma of molecular biology, whereby genetic information flows from DNA (genes) to RNA (transcripts) to protein (products), we have learned a great deal about DNA, RNA, proteins, and the ensuing phenotypic changes. With the advent of high-throughput technologies (1990s), molecular biologists and computer scientists forged critical collaborations to understand the vast amount of data being generated, rapidly escalating gene expression research to the 'omics' level: entire sets of genes (genomes), transcribed RNAs (transcriptomes), and synthesized proteins (proteomes). However, some concessions came to be made for molecular biologists and computer scientists to understand each other-one of the most prevalent being the increasingly widespread use of 'gene' to mean 'RNAs originating from a DNA segment'.

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Reduced brain volumes and more prominent white matter hyperintensities on MRI scans are commonly observed among older adults without cognitive impairment. However, it remains unclear whether rates of change in these measures among cognitively normal adults differ as a function of genetic risk for late-onset Alzheimer's disease, including -ɛ4, -ɛ2 and Alzheimer's disease polygenic risk scores (AD-PRS), and whether these relationships are influenced by other variables. This longitudinal study examined the trajectories of regional brain volumes and white matter hyperintensities in relationship to genotypes ( = 1541) and AD-PRS ( = 1093) in a harmonized dataset of middle-aged and older individuals with normal cognition at baseline (mean baseline age = 66 years, SD = 9.

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Article Synopsis
  • The study investigates how mid-life social relationships influence the link between cerebral small vessel disease (CSVD) markers seen in MRI scans and the risk of developing dementia in older adults.
  • Researchers evaluated participants from the ARIC Study, examining their social support and isolation, and then later assessed CSVD measures and dementia cases over time.
  • Results indicated that poor social relationships intensified the association between white matter hyperintensity volume and dementia risk, with a notably higher hazard ratio for those with weak social ties compared to those with strong relationships.
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Background: Cross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults.

Methods: Longitudinal data [Visit 1 (2004-2009) and Visit 2 (2009-2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits.

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Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

Arterioscler Thromb Vasc Biol

September 2024

Regulatory Biology Laboratory (A.C., T. Lin, T. Le, C.L., S.P.), Salk Institute for Biological Studies, La Jolla, CA.

Article Synopsis
  • Dyslipidemia, a risk factor for cardiovascular disease, can be mitigated by time-restricted feeding (TRF), which limits food intake to a 12-hour window, resulting in reduced weight gain and cholesterol levels in preclinical mouse models.
  • In studies involving mice with LDLR mutations, TRF significantly decreased hypercholesterolemia and atherosclerosis by promoting lipid metabolism and excretion, demonstrating potential benefits for heart health.
  • The findings suggest that TRF could serve as an effective lifestyle intervention for reducing cardiovascular risks, particularly in individuals with LDLR-related conditions, though it may not be effective for those lacking the ApoE protein.
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  • Plasma biomarkers may help identify Alzheimer’s disease and the need for further research across diverse populations and age groups.
  • The study involved 1,525 participants from the Atherosclerosis Risk in Communities (ARIC) study, measuring biomarkers in midlife and late life to assess changes and associations with dementia.
  • Results showed a decline in the Aβ42:Aβ40 ratio and increases in p-tau181, neurofilament light (NfL), and GFAP, indicating a link between these changes and the development of dementia in the participants.
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  • Social connections significantly affect the progression of frailty in older adults, with higher levels of social engagement linked to a reduced risk of developing frailty.* -
  • Increases in loneliness were associated with a higher risk of frailty, indicating that social isolation can negatively impact health outcomes.* -
  • Maintaining and increasing social engagement can help prevent frailty and even reverse its effects, suggesting that fostering social connections is crucial for older adults' wellbeing.*
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  • * The authors advocate for keeping ethnic and race-specific FRAX models in the US, suggesting they should be based on updated data related to fracture and death risks.
  • * The position opposing fixed bone mineral density thresholds is supported by the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), emphasizing the need for equity in fracture risk assessment.
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Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences.

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  • The study focuses on the increased risk of Alzheimer's disease and related disorders (ADRD) among U.S. veterans aged 50 and older, particularly those experiencing homelessness or housing instability.
  • Researchers analyzed data from over 3.2 million veterans utilizing VA services, revealing that homelessness significantly heightens ADRD risk, while HIV/AIDS appears to lower this risk.
  • Findings indicate that hepatitis C and psychiatric disorders are associated with both homelessness and ADRD risk, but their overall impact is minimal when compared to other factors.
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Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited mRNA Stabilization.

Mol Cell Biol

May 2024

Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.

Cellular senescence is a dynamic biological process triggered by sublethal cell damage and driven by specific changes in gene expression programs. We recently identified ANKRD1 (ankyrin repeat domain 1) as a protein strongly elevated after triggering senescence in fibroblasts. Here, we set out to investigate the mechanisms driving the elevated production of ANKRD1 in the early stages of senescence.

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Characterization of age-associated gene expression changes in mouse sweat glands.

Aging (Albany NY)

April 2024

Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.

Evaporation of sweat on the skin surface is the major mechanism for dissipating heat in humans. The secretory capacity of sweat glands (SWGs) declines during aging, leading to heat intolerance in the elderly, but the mechanisms responsible for this decline are poorly understood. We investigated the molecular changes accompanying SWG aging in mice, where sweat tests confirmed a significant reduction of active SWGs in old mice relative to young mice.

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Stoichiometry of long noncoding RNA interactions with other RNAs: Insights from OIP5-AS1.

Wiley Interdiscip Rev RNA

April 2024

Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.

Long noncoding (lnc)RNAs modulate gene expression programs in a range of developmental processes in different organs. In skeletal muscle, lncRNAs have been implicated in myogenesis, the process whereby muscle precursor cells form muscle fibers during embryonic development and regenerate muscle fibers in the adult. Here, we discuss OIP5-AS1, a lncRNA that is highly expressed in skeletal muscle and is capable of coordinating protein expression programs during myogenesis.

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Article Synopsis
  • This study explores how social relationships in mid-life might lower the risk of developing dementia related to brain amyloid levels.
  • Participants from the ARIC study were evaluated for their social support and isolation, with brain amyloid assessed later using advanced imaging.
  • Results indicated that strong social connections in mid-life were linked to a reduced risk of dementia, even though they didn't change the effect of amyloid levels on dementia risk.
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