Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(26)

Published: June 18, 2024

Chaperone-mediated autophagy (CMA) is part of the mammalian cellular proteostasis network that ensures protein quality control, maintenance proteome homeostasis, and changes required for adaptation to stress. Loss one hallmarks aging. CMA decreases with age in multiple rodent tissues human cell types. A decrease lysosomal levels lysosome-associated membrane type 2A (LAMP2A), receptor, has been identified as a main reason declined Here, we report constitutive activation calorie restriction (CR), an intervention extends healthspan, old livers vitro model CR cultured fibroblasts. We found CR-mediated upregulation due improved stability LAMP2A at lysosome membrane. also explore translational value our observations using calorie-restriction mimetics (CRMs), pharmacologically active substances reproduce biochemical functional effects CR. show acute treatment mice CRMs robustly activates several this higher resistance lipid dietary challenges conferred by CRMs. conclude beneficial associated CR/CRMs could be consequence mediated these interventions.

Language: Английский

---

Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Aug. 21, 2024

Bone marrow stromal/stem cells (BMSCs) are generally considered as common progenitors for both osteoblasts and adipocytes in the bone marrow, but show preferential differentiation into rather than under aging, thus leading to senile osteoporosis. Accumulated evidences indicate that rejuvenation of BMSCs by autophagic enhancement delays aging. Here we synthetized demonstrated a novel autophagy activator, CXM102 could induce aged BMSCs, resulting BMSCs. Furthermore, significantly stimulated anabolism, reduced adipocytes, delayed loss middle-age male mice. Mechanistically, promoted transcription factor EB (TFEB) nuclear translocation favored formation vitro vivo. Moreover, decreased serum levels inflammation organ fibrosis, prolonger lifespan Our results indicated be used an inducer rejuvenate shed new lights on strategies osteoporosis healthyspan improvement.

Language: Английский

---

Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

---

CCAAT/Enhancer-Binding Protein Beta Nitration Participates in Hyperhomocysteinemia-Induced Cardiomyocyte Autophagic Flux Blockage by Inhibiting Transcription Factor EB Transcription

Antioxidants and Redox Signaling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Aims: Autophagy is a protective mechanism of cardiomyocytes. Hyperhomocysteinemia (HHcy) elevates oxidative and nitrosative stress levels, leading to an abnormal increase in nitration protein, possibly autophagy regulation However, the regulatory effect HHcy on at post-translational modification level still unclear. Here, we aimed explore transcription factor EB (TFEB) CCAAT/enhancer-binding protein beta (C/EBPβ), transcriptional repressor Tfeb,

Language: Английский

---

Fasting and Autophagy and Its Effect on Health

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Intermittent fasting, a cleansing activity that severely restricts calorie intake, is an effective means of activating autophagy. As dietary pattern, intermittent fasting can delay aging and reduce the risk age-related diseases. helps maintain homeostasis body through series hormonal metabolic changes, protecting variety diseases preventing chronic And it has been shown to improve efficacy weight loss obesity-related non-alcoholic fatty liver disease health indicators. There are still some challenges in area fasting’s effects, further long-term clinical studies needed.

Language: Английский

---

Analysis of factors affecting hospitalization costs in Parkinson disease patients: A retrospective study based on 848 cases

Medicine, Journal Year: 2025, Volume and Issue: 104(7), P. e41540 - e41540

Published: Feb. 14, 2025

This retrospective study aimed to examine hospitalization costs and associated factors for Parkinson disease (PD) patients. A total of 848 PD patients were extracted from the National Neurological Brain Center in Xinjiang, basic demographic information, medical insurance payment, hospital expenses collected. SPSS 26.0 was used univariate analysis performed on number days hospitalization, times hospitalizations, gender, payment method, costs. Correlation using multiple linear regression explore influencing expenses. The average cost 15,515.78 ± 29,667.49 yuan. Diagnosis fees accounted highest proportion (29.50%), followed by material (25.50%) drug (21.20%). with less than 5 hospitalizations main source disease, but 2.83% them had more 10 ( P = .025). Female significantly male patients, much higher those female < .001). increased when they over 60 years old, lower under old .007). effect method did not show a statistical difference .213). There positive correlation between In conclusion, results model suggested that age, length stay, could be as predictive variables

Language: Английский

---

Research progress of cell senescence in Alzheimer's disease: mechanisms and therapy

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177697 - 177697

Published: May 1, 2025

Language: Английский

---

Mitochondria, Autophagy and Inflammation: Interconnected in Aging

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(2), P. 411 - 426

Published: Feb. 21, 2024

Language: Английский

---

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(2), P. 366 - 377

Published: April 3, 2024

Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following growing understanding of the molecular underpinnings their development. This comprehensive review explores mechanisms investigates potential neuroprotective approaches, focusing on activation transcription EB. Recent meta-analyses have demonstrated promising outcomes EB-targeted strategies, such exercise, calorie restriction, rapamycin, metformin, in patients animal models these common diseases. The critically assesses role EB biology during aging, its effects, therapeutic disorders. impact is cell-specific, influencing metabolic reprogramming energy homeostasis neurons through regulation mitochondrial quality control nutrient-sensing pathways. In vascular endothelial cells, controls important processes, cell proliferation, tube formation, nitric oxide levels, thereby inner blood-retinal barrier, angiogenesis, microvasculature. Additionally, affects smooth muscle inhibiting calcification atherogenesis. pigment epithelial modulates functions autophagy, lysosomal dynamics, clearance lipofuscin, promoting photoreceptor survival regulating growth A expression involved neovascularization. These cell-specific significantly encompassing proteostasis, neuronal synapse plasticity, metabolism, microvasculature, inflammation, ultimately offering protection against emphasizes target Therefore, it imperative to obtain well-controlled direct experimental evidence confirm efficacy modulation diseases while minimizing adverse effects.

Language: Английский

---

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6793 - 6793

Published: June 20, 2024

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings aging crucial identify geroprotectors, precisely quantify biological age, propose healthy longevity approaches. This review explores pathways are currently being investigated as intervention targets biomarkers spanning molecular, cellular, systemic dimensions. Interventions target these hallmarks may ameliorate process, with some progressing clinical trials. Biomarkers used estimate aging-associated disease. Utilizing biomarkers, clocks can be constructed predict state abnormal aging, diseases, mortality. Biological age estimation therefore provide basis for fine-grained stratification by predicting all-cause mortality well ahead onset specific thus offering window intervention. Yet, despite technological advancements, challenges persist due individual variability dynamic nature biomarkers. Addressing this requires longitudinal studies robust biomarker identification. Overall, utilizing discover new drug develop opens frontiers medicine. Prospects involve multi-omics integration, machine learning, personalized approaches targeted interventions, promising healthier population.

Language: Английский

---