Telomere attrition and inflammation: the chicken and the egg story

Niveta, J. P. Shirley; Kumar, Mithilesh; Parvathi, Venkatachalam Deepa

doi:10.1186/s43042-022-00335-4

Cited by 6 publications

(5 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, suPAR could be a modulator of prognostic outcomes in SALS patients associated with this molecular phenotype. Telomere length was shorter in cluster three in KCL BrainBank, which despite being non-significant, is also an important trend to investigate as although mounting evidence supports the association between longer telomere length and worsened severity of ALS [ 70 , 71 ], there is also an established link between chronic inflammatory states and telomere shortening in aging and disease [ 72 – 74 ]. Finally, we found that samples in cluster one had a lower age of onset in a combined analysis of KCL BrainBank and TargetALS, which makes sense given that this cluster is linked to neuronal dysfunction and therefore motor neuron degeneration.…”

Section: Discussionmentioning

confidence: 99%

Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data

Marriott,

Kabiljo,

Hunt

et al. 2023

acta neuropathol commun

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) displays considerable clinical and genetic heterogeneity. Machine learning approaches have previously been utilised for patient stratification in ALS as they can disentangle complex disease landscapes. However, lack of independent validation in different populations and tissue samples have greatly limited their use in clinical and research settings. We overcame these issues by performing hierarchical clustering on the 5000 most variably expressed autosomal genes from motor cortex expression data of people with sporadic ALS from the KCL BrainBank (N = 112). Three molecular phenotypes linked to ALS pathogenesis were identified: synaptic and neuropeptide signalling, oxidative stress and apoptosis, and neuroinflammation. Cluster validation was achieved by applying linear discriminant analysis models to cases from TargetALS US motor cortex (N = 93), as well as Italian (N = 15) and Dutch (N = 397) blood expression datasets, for which there was a high assignment probability (80–90%) for each molecular subtype. The ALS and motor cortex specificity of the expression signatures were tested by mapping KCL BrainBank controls (N = 59), and occipital cortex (N = 45) and cerebellum (N = 123) samples from TargetALS to each cluster, before constructing case-control and motor cortex-region logistic regression classifiers. We found that the signatures were not only able to distinguish people with ALS from controls (AUC 0.88 ± 0.10), but also reflect the motor cortex-based disease process, as there was perfect discrimination between motor cortex and the other brain regions. Cell types known to be involved in the biological processes of each molecular phenotype were found in higher proportions, reinforcing their biological interpretation. Phenotype analysis revealed distinct cluster-related outcomes in both motor cortex datasets, relating to disease onset and progression-related measures. Our results support the hypothesis that different mechanisms underpin ALS pathogenesis in subgroups of patients and demonstrate potential for the development of personalised treatment approaches. Our method is available for the scientific and clinical community at https://alsgeclustering.er.kcl.ac.uk.

show abstract

Section: Discussionmentioning

confidence: 99%

Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data

Marriott,

Kabiljo,

Hunt

et al. 2023

acta neuropathol commun

View full text Add to dashboard Cite

show abstract

“…It not only supports telomeres maintenance but also involve in repairing of damaged chromosome ends [37,49]. Telomere length (TL) is influenced by both genetic inheritance and environmental factors, such as reactive oxygen species (ROS) [49][50][51] and inflammation [52][53][54] through different mechanisms as highlighted in Figure 2. Other lifestyle factors contribute to telomere length alterations including nutrition [55][56][57][58].…”

Section: Telomeres and Telomerase Implication In Health And Diseasementioning

confidence: 99%

“…Recent progress in aging research indicates a reciprocal relationship between biological age and susceptibility to disease, suggesting that exposure to infectious diseases can expedite cellular aging [68,75]. Moreover, research has illustrated that telomeres undergo gradual erosion with cell division, eventually leading to cellular senescence or programmed cell death (Figure 4), unless they are sufficiently restored by telomerase [24,52]. Cellular stress orchestrated by parasite infection and immune response can lead to DNA damage and TL shortening.…”

Section: Telomere Length and Telomerase Dynamics In Malariamentioning

confidence: 99%

Telomeres and Telomerase as Promising Targets for Malaria Therapy: A Comprehensive Review

Wakai,

Anzaku,

Afolabi

2024

Preprint

View full text Add to dashboard Cite

Infection with the malaria parasite Plasmodium, remains a major cause of illness and death world-wide. The development of evasion strategies by the parasite from host immunity and its adaptability to antimalarial drugs has raised the urgency for developing new strategies to combat this disease. One promising avenue is targeting telomeres – sequences found at chromosome termini– and telomerase – the enzyme that catalysis synthesis of telomeres using an intrinsic RNA template. As telomeres shorten critically, cells undergo replicative senescence or apoptosis. Plasmodium, lacking telomerase activity in its human stages, exploits alternative mechanisms, accelerating telomere shortening, aging, and immune evasion. Chemical telomerase inhibitors show promise as antimalarials. In this review, we examine the potential of targeting this system in malaria therapy, with telomerase inhibitors offering a novel approach. A systematic search on PubMed using Boolean techniques identified 246 relevant articles from 1985 to March 31, 2024. After filtering, 43 articles met inclusion criteria, supplemented by snowball sampling. The telomerase inhibitor drug strategy is widely applicable against cancer. However, given the drugability of telomerase and the absolute requirement for active telomere maintenance in the vast majority of parasites including plasmodium, telomerase and telomere maintenance could well represent the Achilles heel of the parasite

show abstract

“…Previous studies have shown that telomere length and telomerase activity are negatively affected by exposure to pro-inflammatory cytokines and oxidative stress, two processes associated with cognitive decline [74,75]. Nutritional interventions with PUFAs have proven to be effective in modulating inflammation and telomere length [35,37].…”

Section: Mechanistic Insights and Potential Pathwaysmentioning

confidence: 99%

Dietary fat, telomere length and cognitive function: unravelling the complex relations

Mostafa,

Gutierrez-Tordera,

Mateu-Fabregat

et al. 2023

Current Opinion in Lipidology

View full text Add to dashboard Cite

Purpose of review The review aims to explore the recent evidence on the associations between different dietary fat intake and cognitive function, and to understand the role of telomere length in this relationship. Recent findings Clinical and preclinical studies included in this review suggest that dietary fat intake is associated with cognitive function and telomere length. High intake of saturated fats and trans fats, commonly found in ultra-processed foods, appears to have negative effects on cognitive function and telomere length, while other dietary fats, such as omega-3 polyunsaturated fatty acids and monounsaturated fatty acids are associated with improved cognitive performance and reduced telomere attrition. Controversial results related to omega-6 polyunsaturated fatty acids intake and its impact on cognitive function were found. Dietary fats may affect telomere length and cognition through oxidative stress, inflammation, and insulin resistance. Summary The current review illustrated the relationship between dietary fat and cognitive function by focusing on the role of telomere length as a potential intermediator. More future studies are required, however, in order to develop targeted interventions aimed at preserving cognitive well-being throughout life.

show abstract

Telomere attrition and inflammation: the chicken and the egg story

Cited by 6 publications

References 128 publications

Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data

Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data

Telomeres and Telomerase as Promising Targets for Malaria Therapy: A Comprehensive Review

Dietary fat, telomere length and cognitive function: unravelling the complex relations

Contact Info

Product

Resources

About