Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 10, 2025

Abstract In the context of global ageing, prevalence neurodegenerative diseases and dementia, such as Alzheimer’s disease (AD), is increasing. However, current symptomatic disease-modifying therapies have achieved limited benefits for in clinical settings. Halting progress neurodegeneration cognitive decline or even improving impaired cognition function are clinically meaningful goals treatments diseases. Ageing primary risk factor their associated comorbidities, vascular pathologies, elderly individuals. Thus, we aim to elucidate role ageing from perspective a complex system, which brain core peripheral organs tissues form holistic network support functions. During progressive deterioration structure entire body hampers its active adaptive responses various stimuli, thereby rendering individuals more vulnerable Consequently, propose that prevention treatment should be grounded antiageing rejuvenation means complemented by interventions targeting disease-specific pathogenic events. This integrated approach promising strategy effectively prevent, pause slow down progression

Язык: Английский

---

Mid‐life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants

Aging Cell, Год журнала: 2023, Номер 22(7)

Опубликована: Май 30, 2023

Abstract Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging‐related diseases, including Alzheimer's disease related dementias (AD/ADRD). The objective this study was assess associations leukocyte telomere length (TL) with AD/ADRD early markers AD/ADRD, cognitive performance brain magnetic resonance imaging (MRI) phenotypes. Data from European‐ancestry participants in the UK Biobank ( n = 435,046) were used evaluate whether mid‐life TL associated incident over a mean follow‐up 12.2 years. In subsample without data 43,390), we MRI phenotypes AD or vascular dementia pathology. Longer lower risk (adjusted Hazard Ratio [aHR] per SD 0.93, 95% CI 0.90–0.96, p 3.37 × 10 −7 ). also better specific domains, larger hippocampus volume, total volume white matter hyperintensities, higher fractional anisotropy diffusivity fornix. conclusion, longer inversely impairment, structural lesions toward development AD/ADRD. However, relationships between genetically determined outcomes above not statistically significant based on results Mendelian randomization analysis results. Our findings add literature prioritizing for causality needs ascertained mechanistic studies.

Язык: Английский

---

Role of Glucose Metabolism in the Effects of Serum Metals on Telomere Length: Findings in Chinese Diabetic Population

Biological Trace Element Research, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Язык: Английский

---

The impact of telomere length on the risk of idiopathic normal pressure hydrocephalus: a bidirectional Mendelian randomization study

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 26, 2024

Abstract Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one the hallmarks aging. Whereas genetic contribution TL to iNPH incompletely understood. We aimed investigate causal relationship between and through Mendelian randomization (MR) analysis. respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) 20 eligible SNPs for MR result analysis showed that genetically predicted longer was significantly associated with a reduced odd (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447–0.899, p 0.011). association remained consistent in multivariable (OR 0.530 CI 0.327–0.860, 0.010). However, there no evidence causally 1.000 0.996–1.004, 0.955). Our study reveals potential etiology iNPH, increased might be risk iNPH.

Язык: Английский

---

The mechanisms, hallmarks, and therapies for brain aging and age-related dementia

Science Bulletin, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

---

Telomere Length, Brain Imaging-Derived Phenotypes, and Alzheimer’s Disease: Mendelian Randomization Analysis

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

Язык: Английский

---

Association between the development of vibration disease and a decrease in the relative length of telomeres among employees of Bashkortostan enterprises

Russian Journal of Occupational Health and Industrial Ecology, Год журнала: 2025, Номер 65(3), С. 202 - 208

Опубликована: Апрель 7, 2025

Vibration disease (VD) is an occupational that develops with prolonged exposure to industrial vibrations of different frequencies. Previously, the effect vibration on human aging was shown, measured basis physiological indicators. Measuring telomere length most common indicator a person's biological age, which believed reflect difference in rate. Telomeres are non-coding regions heterochromatin and serve protect ends chromosomes from sticking together gene erosion. The study aims estimate age employees suffering by determining relative telomeres (RLT). To conduct study, specialists received biomaterials 51 people aged 35 60 years, who were examined at Ufa Research Institute Occupational Health Human Ecology. participants divided into groups depending diagnosis type exposure. Determination carried out using real-time polymerase chain reaction (RT-PCR) method. researchers performed statistical analysis scipy.stats package Python. found statistically significant decrease group workers compared healthy workers. An exposed various types revealed general other studied. development associated average length. This biomarker also shows differences nature exposure: greater than local vibration. Limitations. disadvantages work include lack data working conditions. It not possible obtain magnitude impact vibration, did allow quantifying its telomeres. Also, does take account accompanying harmful production factors, since their heterogeneity small sample size for each factor analysis. additional tests, such as level cortisol hormones stress response. worth noting under regression compare effects gender, characteristics disease.

Язык: Английский

---

Potential roles of telomeres and telomerase in neurodegenerative diseases

Ageing and Neurodegenerative Diseases, Год журнала: 2024, Номер 4(1)

Опубликована: Янв. 19, 2024

Telomeres, essential DNA-protein complexes located at chromosome ends, play a critical role in preventing fusion, recombination, and degradation, thus ensuring genomic stability. When telomeres reach limiting shortened length, they will activate DNA damage checkpoints, stop cell division trigger replicative senescence. Telomerase is composed of RNA protein, which can synthesize repeat sequences, elongate telomeres. Studies have shown that telomere length (TL) telomerase activity are closely involved aging, aging-related degenerative diseases, tumors. Neurodegenerative diseases (NDDs) one the major caused by both genetic environmental factors, characterized insidious onset, difficult diagnosis, irreversible disease progression, lack effective treatments, brings heavy burden to society families. Currently, many studies noted variations leukocyte (LTL) NDDs, suggesting vital for NDD pathogenesis. This review explores relationship between TL examines as potential therapeutic target, discusses emerging biomarkers intervention strategies diagnosis treatment.

Язык: Английский

---

Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner

Aging Cell, Год журнала: 2024, Номер 23(5)

Опубликована: Март 7, 2024

Abstract Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of linked to AD pathogenesis remain poorly understood. Here, we report first characterization age‐ and sex‐related trajectories telomere length (TL) micronuclei APP/PS1 mice model wild‐type (WT) controls (C57BL/6). TL was measured brain (prefrontal cortex, cerebellum, pituitary gland, hippocampus), colon skin, MN bone marrow 6‐ 14‐month‐old mice. Variation attributable tissue type, age, genotype and, a lesser extent, sex. Compared WT, had significantly shorter baseline across all examined tissues. inversely associated age both genotypes shortening accelerated APP/PS1. Age‐related increase observed but We integrated data on cognition performance amyloidosis. were linearly correlated or Aβ 40 42 levels greater extent These associations dominantly driven by females. Together, our findings provide foundational knowledge infer during progression, strongly support attrition micronucleation are tightly female‐biased manner.

Язык: Английский

---

Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease

Age and Ageing, Год журнала: 2024, Номер 53(10)

Опубликована: Окт. 1, 2024

Abstract Background Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification reliable biomarkers ageing is essential to prevent accelerated cognitive impairment. Methods We selected 317 non-smoking ‘Prevención con Dieta Mediterránea-Plus’ (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) metabolic syndrome from two trial centres who were following lifestyle intervention. measured TL and function at baseline after 3 4 years follow-up, respectively. Associations between or 3-year changes in 4-year analysed using multivariable regression models. Results Baseline was not performance. Nevertheless, longer improved Executive Function domain (β: 0.29; 95%CI: 0.12 0.44; P < 0.001) Global 0.19; 0.05 0.34; = 0.010). Besides, positive association found animal version Verbal Fluency Test 0.33; 0.52; 0.002). By contrast, years. Conclusions Longer could protect decline be used as useful biomarker an older Mediterranean population risk cardiovascular disease

Язык: Английский

---