Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2796 - 2796
Published: Dec. 9, 2024
Cellular senescence has emerged as a fascinating frontier in biological research and now presents profound implications across diverse fields, from aging to cancer therapy [...]
Language: Английский
ESC Heart Failure, Journal Year: 2024, Volume and Issue: unknown
Published: July 22, 2024
Abstract Systemic aging influences various physiological processes and contributes to structural functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a diastolic function, atrial dilation, fibrillation, myocardial fibrosis amyloidosis, elevating susceptibility chronic heart failure (HF) the elderly. Age‐related dysfunction stems from prolonged exposure genomic, epigenetic, oxidative, autophagic, inflammatory regenerative stresses, along with accumulation senescent cells. Concurrently, age‐related changes vascular system, attributed endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress inflammation, impose additional strain on heart. Dysregulated mechanosignalling nitric oxide signalling play critical roles associated HF. Metabolic drives intricate shifts glucose lipid metabolism, leading insulin resistance, mitochondrial within cardiomyocytes. contribute contractility, ultimately propelling low‐grade conjunction senescence‐associated secretory phenotype, aggravates age by promoting immune cell infiltration into myocardium, fostering This is further exacerbated comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes kidney (CKD). CAD atherosclerosis induce ischaemia adverse remodelling, while hypertension hypertrophy fibrosis. Obesity‐associated inflammation dyslipidaemia create profibrotic environment, whereas diabetes‐related metabolic disturbances impair function. CKD‐related fluid overload, electrolyte imbalances uraemic toxins exacerbate HF through systemic neurohormonal renin‐angiotensin‐aldosterone system (RAAS) activation. Recognizing as modifiable process has opened avenues target both lifestyle interventions therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological remodelling elderly countering linked HF, such senescence declining cardiomyocyte regeneration. Dietary plant‐based ketogenic diets, caloric restriction macronutrient supplementation are instrumental maintaining energy balance, reducing adiposity addressing micronutrient Therapeutic advancements targeting underway. Key approaches senomorphics senolytics limit senescence, antioxidants stress, anti‐inflammatory drugs interleukin (IL)‐1β inhibitors, rejuvenators nicotinamide riboside, resveratrol sirtuin (SIRT) activators autophagy enhancers metformin sodium‐glucose cotransporter 2 (SGLT2) all which offer potential preserving function alleviating burden.
Language: Английский
Citations
11
Aging Cell, Journal Year: 2024, Volume and Issue: 23(4)
Published: March 7, 2024
Unlike chronological age, biological age is a strong indicator of health an individual. However, the molecular fingerprint associated with ill-defined. To define high-resolution signature we analyzed metabolome, circulating senescence-associated secretome (SASP)/inflammation markers and interaction between them, from cohort healthy rapid agers. The balance two fatty acid oxidation mechanisms, β-oxidation ω-oxidation, extent functional aging. Furthermore, panel 25 metabolites, Healthy Aging Metabolic (HAM) index, predicted agers regardless gender race. HAM index was also validated in independent cohort. Causal inference machine learning implied three β-cryptoxanthin, prolylhydroxyproline, eicosenoylcarnitine as putative drivers Multiple SASP were elevated Together, our findings reveal that network metabolic pathways underlie aging, could serve predictor phenotypic aging humans.
Language: Английский
Citations
10
The Journals of Gerontology Series A, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 14, 2025
Abstract Chronological age is a major risk factor for numerous diseases. However, chronological does not capture the complex biological aging process. difference between and biologically driven could be more informative in reflecting health status. Here, we set out to develop metabolomic prediction model by applying ridge regression bootstrapping with 826 metabolites (678 endogenous 148 xenobiotics) measured an untargeted platform relatively healthy blood donors aged 18-75 years from INTERVAL study (N=11,977;50.2% men). After internal validation, models demonstrated high performance adjusted R2 of 0.83 using all 0.82 only metabolites. The former was significantly associated obesity cardiovascular disease (CVD) NEO (N=599;47.0% men; range=45-65) due contribution medication derived metabolites—namely salicylate ibuprofen—and environmental exposures such as cotinine. Additional were developed men women separately. had (R²=0.85 0.86) but shared moderate correlation 0.72. Furthermore, observed 163 sex-dimorphic metabolites, including threonine, glycine, cholesterol, androgenic progesterone-related Our strongest predictors across novel included hydroxyasparagine (Model Endo+Xeno β=4.74), vanillylmandelate (β=4.07), 5,6-dihydrouridine (β=-4.2). presents robust that reveals distinct sex-based age-related metabolic patterns illustrates value xenobiotic enhance accuracy.
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: April 10, 2025
Introduction: Aging is associated with significant metabolic alterations that contribute to cellular senescence and age-related functional decline. As individuals age, an increased prevalence of oral diseases a gradual decline in functions are observed. However, the shifts underlying mucosal aging remain unexplored. Methods: We initially conducted histological analyses on tongues from young (4-week-old), adult (4-month-old) old (20-month-old) C57BL/6 mice identify tongue mucosa. Subsequently, metabolomics analysis was performed characterize profiles mouse across these age groups biomarkers aging. Then we validate anti-senescence effect carnosine investigate its mechanisms using tert-butyl hydroperoxide (tBHP)-induced model vitro. Finally, human saliva blood were explore associations between levels systemic Results: Compared mice, observed epithelial atrophy accumulation senescent cells mucosa mice. After that, found differences among young, adult, tongues. Carnosine identified as potential biomarker aging, declined significantly age. Consistently, synthase 1 (CARNS1) activity decreased, carnosinase 2 (CNDP2) Furthermore, protected tBHP-induced by reducing oxidative stress, mitigating DNA damage, downregulating Nrf2/HO-1 pathway. In humans, salivary also diseases. Discussion: Our findings reveal dynamic reprogramming during natural highlight dual role both therapeutic target for combating degeneration. These insights support development novel carnosine-based interventions preserve function, prevent diseases, improve health population, thereby advancing healthy
Language: Английский
Citations
0
Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 19, 2024
Scope Polyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti‐inflammatory, and anti‐cancer effects. In recent reports, phytoestrogens attenuate age‐related diseases; however, pro‐longevity effects in healthy models mammals remain unknown. As longevity research demonstrates transcriptomic signatures human blood, current study hypothesizes that phytoestrogen‐supplemented diet may induce changes gene expression ultimately confer benefits. Methods results present study, RNA sequencing is conducted to determine transcriptome‐wide whole blood of rats consuming diets supplemented with phytoestrogens. Ortholog cell deconvolution applied analyze omics data. The discovered PTS leads landscape PTS‐target genes associated functions counteracting hallmarks aging, genomic instability, epigenetic alterations, compromised autophagy, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular interaction, loss proteostasis. These bridge together under anti‐inflammatory through multiple pathways, immunometabolism, where cellular metabolism (e.g., ribosome biogenesis) impact immune system. Conclusion findings provide a rationale pre‐clinical clinical studies encourage investigations on maintaining homeostasis, decelerating process improving conditions chronic inflammation.
Language: Английский
Citations
2
Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1476 - 1476
Published: Nov. 20, 2024
Accumulation of senescent endothelial cells (ECs) in vasculature represents a key step the development vascular aging and ensuing age-related diseases. Given that removal ECs may prevent disease improve health wellbeing, discovery novel biomarkers effectively identify is particular importance. As crucial elements for biological pathways reliable bioindicators cellular processes, metabolites demand attention this context. Using human brain microvascular (HBMECs) displaying secretory phenotype significant morphological, nuclear, enzymatic changes compared to their young counterparts, study has shown HBMECs lose characteristics as evidenced by disappearance CD31/PECAM-1 from interendothelial cell junctions. The metabolic profiling versus also indicates differences glucose, glutamine, fatty acid metabolism. analysis intracellular secreted proposes L-proline, L-glutamate, NAD
Language: Английский
Citations
2
The Journal of Cardiovascular Aging, Journal Year: 2024, Volume and Issue: 4(4)
Published: Dec. 31, 2024
Acetyltransferases are enzymes that catalyze the transfer of an acetyl group to a substrate, modification referred as acetylation. Loss-of-function variants in genes encoding acetyltransferases can lead congenital disorders, often characterized by intellectual disability and heart muscle defects. Their activity is influenced dietary nutrients alter coenzyme A levels, key cofactor. Cardiovascular diseases, including ischemic, hypertensive, diabetic diseases - leading causes mortality elderly largely attributed prolonged lifespan growing prevalence metabolic syndrome. thus serve crucial link between lifestyle modifications, cardiometabolic disease, aging through both epigenomic non-epigenomic mechanisms. In this review, we discuss roles relevance acetyltransferases. While sirtuin family deacetylases has been extensively studied longevity, particularly fasting-mediated NAD+ metabolism, recent research brought attention essential health aging-related pathways, cell proliferation, DNA damage response, mitochondrial function, inflammation, senescence. We begin with overview acetyltransferases, classifying them domain structure, canonical non-canonical lysine N-terminal sialic acid O-acetyltransferases. then advances understanding acetyltransferase-related pathologies, focusing on cardiovascular disease aging, explore their potential therapeutic applications for promoting older individuals.
Language: Английский
Citations
2
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Journal Year: 2024, Volume and Issue: 20(5), P. 343 - 348
Published: Sept. 27, 2024
Background. Aging is associated with changes in organs and systems that contribute to the development of age-related pathology. Accelerated aging characterized by metabolic disorders create conditions for type 2 diabetes (T2D). The T2D older individuals can be considered as accelerated aging. In cases combined cardiovascular pathology elderly, there a cardiometabolic To assess rate this process, it advisable use formula calculating biological age (BA) based on parameters. case, partial BA called age. Its value will degree hemodynamic disturbances. purpose study was develop simple method assessing calculate Materials methods. A total 155 practically healthy (without T2D, cardiovascular, renal pathology) aged 30 80 years were examined, 23 patients without comorbidities, 92 concomitant hypertension, 55 hypertension ischemic heart disease, 72 chronic kidney 25 peripheral neuropathy. All participants had anthropometric measurements taken, systolic diastolic blood pressure measured. Serum levels cholesterol, triglycerides, low- high-density lipoprotein creatinine, glomerular filtration rate, aspartate aminotransferase, alanine albuminuria determined. stepwise multiple regression using StatSoft Statistica package (USA) used mathematical model. assessed difference between chronological Results. Calculation our showed average absolute error calculation 7.79 ± 0.49 years. Correction systematic significantly increased accuracy (R2 = 0.78; p < 0.00001; 4.80 0.32 years). exceeded their age, 12.7 1.9 comorbidities from 14.5 2.0 19.1 1.5 presence or complications. obtained result indicates an risk developing diseases, chronic polyneuropathy. Conclusion. developed us has sufficiently high predict combination
Language: Английский
Citations
0
Procedia Computer Science, Journal Year: 2024, Volume and Issue: 246, P. 1963 - 1972
Published: Jan. 1, 2024
Language: Английский
Citations
0
Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2796 - 2796
Published: Dec. 9, 2024
Cellular senescence has emerged as a fascinating frontier in biological research and now presents profound implications across diverse fields, from aging to cancer therapy [...]
Language: Английский
Citations
0