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Advances in Gerontology = Uspekhi... 2024Multi-omics methods for analysing postgenomic data have become firmly established in the tools of molecular gerontology only in recent years, since previously there were... (Review)
Review
Multi-omics methods for analysing postgenomic data have become firmly established in the tools of molecular gerontology only in recent years, since previously there were no comprehensive integrative approaches adequate to the task of calculating biological age. This paper provides an overview of existing papers on multi-omics integrative approaches in calculating the biological age of a human. An analysis of the most common options for integrating methylomic, transcriptomic, proteomic, microbiomic and metabolomic datasets was carried out. We defined (1) concatenation (machine learning), in which models are developed using a concatenated data matrix, formed by combining multiple omics data sets; (2) fusion model approaches that create multiple intermediate submodels for different omics data to then build a final integrated model from the various intermediate submodels; and (3) transformation methods (via artificial intelligence) that first transform each of the single omics data sets into core plots or matrices, and then combine them all into one graph before building an integral complex model. It is unlikely that multi-omics approaches will find application in anti-aging personalized medicine, but they will undoubtedly deepen and expand the understanding of the fundamental processes standing behind the phenomenon of the biological aging clocks.
Topics: Humans; Aging; Proteomics; Metabolomics; Genomics; Computational Biology; Machine Learning; Multiomics
PubMed: 38944768
DOI: No ID Found -
Journal of the American Geriatrics... Jun 2024Sensory disability in older adults is associated with increased rates of depressive symptoms and loneliness. Here, we examined the impact of hearing, vision, and...
BACKGROUND
Sensory disability in older adults is associated with increased rates of depressive symptoms and loneliness. Here, we examined the impact of hearing, vision, and olfaction disability on mental health outcomes in older US adults.
METHODS
We studied respondents from the first three rounds (2005/6, 2010/11, and 2015/16) of the National Social Life, Health and Aging Project, a nationally representative, longitudinal study of older US adults. Sensory function was assessed by structured interviewer ratings (hearing and vision) and objective assessment (olfaction). Cox proportional hazards models and one degree of freedom tests for trend were utilized to analyze the relationships between sensory disability and self-rated mental health, frequent depressive symptoms, frequent perceived stress, frequent anxiety symptoms, and frequent loneliness symptoms over time, adjusting for demographics, health behaviors, comorbidities, and cognitive function.
RESULTS
We analyzed data from 3940 respondents over 10 years of follow-up. A greater number of sensory disabilities was associated with greater hazard of low self-rated mental health, frequent depressive symptoms, frequent perceived stress, and frequent loneliness symptoms over time (p ≤ 0.003, all). After adjusting for covariates, older adults with a greater number of sensory disabilities had greater hazard of low self-rated mental health (HR = 1.22, CI = [1.08, 1.38], p = 0.002) and loneliness symptoms (HR = 1.13, CI = [1.05, 1.22], p = 0.003) over time in our tests for trend. In our Cox proportional hazards model, older adults with vision disability had greater hazard of low self-rated mental health (HR = 1.34, 95% CI = [1.05, 1.72], p = 0.02) and loneliness symptoms (HR = 1.21, CI = [1.04, 1.41], p = 0.01).
CONCLUSIONS
Older US adults with greater numbers of sensory disabilities face worse subsequent mental health. Future longitudinal studies dissecting the relationship of all five classical senses will be helpful in further understanding how improving sensory function might improve mental health in older adults.
PubMed: 38944677
DOI: 10.1111/jgs.19056 -
Nature Communications Jun 2024JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the...
JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the Drosophila intestine, the TNF-type ligand, Eiger (Egr), is expressed exclusively by intestinal stem cells (ISCs) and enteroblasts (EBs), where it is induced by stress and during aging. Egr preferentially activates JNK signaling in a paracrine fashion in differentiated enterocytes (ECs) via its receptor, Grindelwald (Grnd). N-glycosylation genes (Alg3, Alg9) restrain this activation, and stress-induced downregulation of Alg3 and Alg9 correlates with JNK activation, suggesting a regulatory switch. JNK activity in ECs induces expression of the intermembrane protease Rhomboid (Rho), driving secretion of EGFR ligands Keren (Krn) and Spitz (Spi), which in turn activate EGFR signaling in progenitor cells (ISCs and EBs) to stimulate their growth and division, as well as to produce more Egr. This study uncovers an N-glycosylation-controlled, paracrine JNK-EGFR-JNK feedforward loop that sustains ISC proliferation during stress-induced gut regeneration.
Topics: Animals; Drosophila Proteins; ErbB Receptors; Intestines; MAP Kinase Signaling System; Drosophila melanogaster; Enterocytes; Stem Cells; Intestinal Mucosa; Drosophila; Glycosylation; Receptors, Invertebrate Peptide; Cell Proliferation; JNK Mitogen-Activated Protein Kinases; Signal Transduction; Cell Communication; Cell Differentiation; Epidermal Growth Factor; Membrane Proteins
PubMed: 38944657
DOI: 10.1038/s41467-024-49786-w -
Trends in Immunology Jun 2024Basophils, rare granulocytes, have long been acknowledged for their roles in type 2 immune responses. However, the mechanisms by which basophils adapt their functions to... (Review)
Review
Basophils, rare granulocytes, have long been acknowledged for their roles in type 2 immune responses. However, the mechanisms by which basophils adapt their functions to diverse mammalian microenvironments remain unclear. Recent advancements in specific research tools and single-cell-based technologies have greatly enhanced our understanding of basophils. Several studies have shown that basophils play a role in maintaining homeostasis but can also contribute to pathology in various tissues and organs, including skin, lung, and others. Here, we provide an overview of recent basophil research, including cell development, characteristics, and functions. Based on an increasing understanding of basophil biology, we suggest that the precise targeting of basophil features might be beneficial in alleviating certain pathologies such as asthma, atopic dermatitis (AD), and others.
PubMed: 38944621
DOI: 10.1016/j.it.2024.05.009 -
Seizure Jun 2024The unique patho-clinical entity of late-onset epilepsy (LOE), distinguished by its distinct natural history, from its onset to the prognosis it portends, necessitates... (Review)
Review
The unique patho-clinical entity of late-onset epilepsy (LOE), distinguished by its distinct natural history, from its onset to the prognosis it portends, necessitates specialized care. We lack a universally accepted definition, but LOE is typically identified as epilepsy onset after the age of 60 or 65. Unlike epilepsy in younger individuals, LOE is almost by default focal in origin, secondary to acquired etiologies, and presents unique diagnostic and management challenges due to its atypical semiology, higher comorbidity burden, frailty, and increased risks of subsequent stroke and dementia. LOE clinics have been established to address these challenges, providing a multidisciplinary approach to optimize outcomes in patients with new-onset seizures beyond the fifth decade of life. LOE clinics are essential for comprehensive care, offering not only seizure management but also monitoring and addressing associated comorbidities. The care model involves collaboration among neurologists, primary care providers, cardiologists, mental health professionals, and social workers to manage LOE patients' complex needs effectively. The prevalence of cognitive dysfunction in LOE patients underscores the need for regular cognitive assessments and interventions. Biomarker research, particularly involving amyloid beta, offers promising avenues for early diagnosis and a better understanding of the interplay between LOE and Alzheimer's disease. Establishing LOE clinics in major referral centers can enhance provider expertise, improve patient outcomes, and facilitate research to advance diagnostic and therapeutic strategies. In conclusion, LOE clinics play a critical role in addressing the multifaceted needs of older adults with epilepsy, tailored to local resources and challenges, thus enhancing epilepsy care in an aging global population.
PubMed: 38944548
DOI: 10.1016/j.seizure.2024.06.026 -
The Surgical Clinics of North America Aug 2024Adrenal incidentalomas have increased due to advanced and more sensitive imaging modalities, their increased utilization, and the aging population. Most adrenal... (Review)
Review
Adrenal incidentalomas have increased due to advanced and more sensitive imaging modalities, their increased utilization, and the aging population. Most adrenal incidentalomas are nonfunctional and benign, but a subset of patients has functional and/or malignant tumors. The evaluation of patients with an adrenal incidentaloma involves addressing 2 clinical questions: (1) Is the tumor functional? (2) Is the tumor malignant? A careful history and physical examination focused on signs and symptoms of adrenal functional tumors, biochemical testing, and imaging features are the cornerstone in the evaluation of patients with an adrenal incidentaloma.
Topics: Humans; Adrenal Gland Neoplasms; Incidental Findings; Diagnosis, Differential; Tomography, X-Ray Computed
PubMed: 38944503
DOI: 10.1016/j.suc.2024.02.012 -
Delirium in the US: Results from 2023 cross-sectional World Delirium Awareness Day prevalence study.Journal of the Academy of... Jun 2024Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia.
IMPORTANCE
Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia.
OBJECTIVES
To describe the prevalence of clinically documented delirium in the United States on World Delirium Awareness Day 2023.
DESIGN
Sub-analysis of a prospective, cross-sectional, online, international survey.
SETTING
All healthcare settings were eligible with the exception of operating rooms and outpatient clinics.
PARTICIPANTS
Healthcare clinicians, administrators, and researchers completed the survey.
MAIN OUTCOME AND MEASURE
Prevalence of clinically documented delirium at 8:00 a.m. and 8:00 p.m. on March 15, 2023. Secondary outcomes were related to healthcare delivery. Descriptive statistics are reported. Differences between unit types (non-ICU vs ICU) were examined for all outcomes.
RESULTS
Ninety-one hospital units reported on 1,318/1,213 patients. The prevalence of clinically documented delirium was 16.4% (n=216/1,318) at 8:00 a.m., 17.9% (n=217/1,213) at 8:00 p.m. (p= 0.316) and significantly differed between age groups, reported discipline, unit, and hospital types. Significant differences were identified between non-ICU and ICU settings in the use of delirium-related protocols, non-pharmacologic and pharmacologic management, educational processes, and barriers to evidence-based delirium care.
CONCLUSION
To our knowledge, this is the first epidemiologic survey of clinically documented delirium across two time points in the U.S.. Delirium remains a significant burden and challenge for healthcare systems. The high percentage of units using delirium management protocols suggests administrator and clinician awareness of evidence-based strategies for its detection and mitigation. We provide recommendations for future studies and quality improvement projects to improve clinical recognition and management of delirium.
PubMed: 38944277
DOI: 10.1016/j.jaclp.2024.06.005 -
Neuroscience and Biobehavioral Reviews Jun 2024Cognitive challenges and brain structure variations are common in autism spectrum disorder (ASD) but are rarely explored in middle-to-old aged autistic adults. Cognitive... (Review)
Review
Cognitive challenges and brain structure variations are common in autism spectrum disorder (ASD) but are rarely explored in middle-to-old aged autistic adults. Cognitive deficits that overlap between young autistic individuals and elderlies with dementia raise an important question: does compromised cognitive ability and brain structure during early development drive autistic adults to be more vulnerable to pathological aging conditions, or does it protect them from further decline? To answer this question, we have synthesized current theoretical models of aging in ASD and conducted a systematic literature review (Jan 1, 1980 - Feb 29, 2024) and meta-analysis to summarize empirical studies on cognitive and brain deviations in middle-to-old aged autistic adults. We explored findings that support different aging theories in ASD and addressed study limitations and future directions. This review sheds light on the poorly understood consequences of aging question raised by the autism community to pave the way for future studies to identify sensitive and reliable measures that best predict the onset, progression, and prognosis of pathological aging in ASD.
PubMed: 38944227
DOI: 10.1016/j.neubiorev.2024.105782 -
Pharmacological Research Jun 2024The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. The pathogenesis of cardiovascular disease is... (Review)
Review
The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. The pathogenesis of cardiovascular disease is complex and not fully understood, and the physiological function of the heart is inextricably linked to well-regulated cardiac muscle movement. Myosin light chain kinase (MLCK) is essential for myocardial contraction and diastole, cardiac electrophysiological homeostasis, vasoconstriction of vascular nerves and blood pressure regulation. In this sense, MLCK appears to be an attractive therapeutic target for cardiac diseases. MLCK participates in myocardial cell movement and migration through diverse pathways, including regulation of calcium homeostasis, activation of myosin light chain phosphorylation, and stimulation of vascular smooth muscle cell contraction or relaxation. Recently, phosphorylation of myosin light chains has been shown to be closely associated with the activation of myocardial exercise signaling, and MLCK mediates systolic and diastolic functions of the heart through the interaction of myosin thick filaments and actin thin filaments. It works by upholding the integrity of the cytoskeleton, modifying the conformation of the myosin head, and modulating innervation. MLCK governs vasoconstriction and diastolic function and is associated with the activation of adrenergic and sympathetic nervous systems, extracellular transport, endothelial permeability, and the regulation of nitric oxide and angiotensin II. Additionally, MLCK plays a crucial role in the process of cardiac aging. Multiple natural products/phytochemicals and chemical compounds, such as quercetin, cyclosporin, and ML-7 hydrochloride, have been shown to regulate cardiomyocyte MLCK. The MLCK-modifying capacity of these compounds should be considered in designing novel therapeutic agents. This review summarizes the mechanism of action of MLCK in the cardiovascular system and the therapeutic potential of reported chemical compounds in cardiac diseases by modifying MLCK processes.
PubMed: 38944220
DOI: 10.1016/j.phrs.2024.107276 -
Free Radical Biology & Medicine Jun 2024Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the...
Reactive oxygen species in skeletal muscle injury, fatigue, regeneration and ageing: In memory of John Faulkner The role of zinc and matrix metalloproteinases in myofibrillar protein degradation in critical illness myopathy.
Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the activation of matrix metalloproteinases (MMPs) in skeletal muscle exposed to the intensive care unit (ICU) condition (immobilization and mechanical ventilation). ICU patients exposed to 12 days ICU condition were followed longitudinally with six repeated muscle biopsies while they showed a progressive preferential myosin loss, i.e., the hallmark of Critical Illness Myopathy (CIM), in parallel with the activation of Zn-transporters. In this study, we have revisited the expression of Zn-transporters and the activation of MMPs in clinical as well as in experimental studies using an established ICU model. MMPs are a group Zn-dependent endopeptidases which do not only target and cleave extracellular proteins but also intracellular proteins including multiple sarcomeric proteins. MMP-9 is of specific interest since the hallmark of CIM, the preferential myosin loss, has also been reported in dilated cardiomyopathy and coupled to MMP-9 activation. Transcriptional activation of Zn-transporters was observed in both clinical and experimental studies as well as the activation of MMPs, in particular MMP-9, in various limb and respiratory muscles in response to long-term exposure to the ICU condition. The activation of Zn-transporters was paralleled by increased Zn levels in skeletal muscle which in turn showed a negative linear correlation with the preferential myosin loss associated with CIM, offering a potential intervention strategy. Thus, activation of Zn-transporters, increased intramuscular Zn levels, and activation of the Zn-dependent MMPs are forwarded as a probable mechanism involved in CIM pathophysiology. These effects were confirmed in different rat strains subjected to a model of CIM and exacerbated by old age. This is of specific interest since old age and muscle wasting are the two factors most strongly associated with ICU mortality.
PubMed: 38944212
DOI: 10.1016/j.freeradbiomed.2024.06.022