Breaking down causes, consequences, and mediating effects of telomere length variation on human health

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: May 17, 2024

Abstract Background Telomeres form repeated DNA sequences at the ends of chromosomes, which shorten with each cell division. Yet, factors modulating telomere attrition and health consequences thereof are not fully understood. To address this, we leveraged data from 326,363 unrelated UK Biobank participants European ancestry. Results Using linear regression bidirectional univariable multivariable Mendelian randomization (MR), elucidate relationships between leukocyte length (LTL) 142 complex traits, including diseases, biomarkers, lifestyle factors. We confirm that telomeres age show a stronger decline in males than females, these contributing to majority 5.4% LTL variance explained by phenome. MR reveals 23 traits LTL. Smoking cessation high educational attainment associate longer LTL, while weekly alcohol intake, body mass index, urate levels, female reproductive events, such as childbirth, shorter also identify 24 affected risk for cardiovascular, pulmonary, some autoimmune diseases being increased short other conditions cancers. Through MR, may partially mediate impact attainment, childbirth on proxied lifespan. Conclusions Our study sheds light modulators, consequences, mediatory role telomeres, portraying an intricate relationship lifestyle, socio-economic

Language: Английский

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Recent Advances in DNA Systems for In Situ Telomerase Activity Detection and Imaging

Chemosensors, Journal Year: 2025, Volume and Issue: 13(1), P. 17 - 17

Published: Jan. 15, 2025

Telomeres play a key role in maintaining chromosome stability and cellular aging. They consist of repetitive DNA sequences that protect ends regulate cell division. Telomerase is reverse transcriptase enzyme counteracts the natural shortening telomeres during division by extending them. Its activity pivotal stem cells cancer but absent most normal somatic cells. Recent advances biosensor technologies have facilitated situ detection telomerase activity, which essential for understanding its aging cancer. Techniques such as fluorescence, electrochemistry, nanotechnology are now being employed to monitor living cells, providing real-time insights into processes. DNA-based biosensors, especially those incorporating molecular beacons, walkers, logic gates, shown promise enhancing sensitivity specificity imaging. These approaches also facilitate simultaneous analysis related pathways, offering potential applications early precision therapies. This review explores recent developments intracellular imaging, highlighting innovative DNA-functionalized nanoparticles multi-channel systems, offer non-invasive, complex environments.

Language: Английский

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Association of traffic volume and leukocyte telomere length of Malaysian populations living in urban and rural areas

Environmental Chemistry and Ecotoxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Disentangling mechanisms behind the pleiotropic effects of proximal 16p11.2 BP4-5 CNVs

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: 111(11), P. 2347 - 2361

Published: Sept. 26, 2024

Whereas 16p11.2 BP4-5 copy-number variants (CNVs) represent one of the most pleiotropic etiologies genomic syndromes in both clinical and population cohorts, mechanisms leading to such pleiotropy remain understudied. Identifying 73 deletion 89 duplication carrier individuals among unrelated White British UK Biobank participants, we performed a phenome-wide association study (PheWAS) between region's copy number 117 complex traits diseases, mimicking four dosage models. Forty-six phenotypes (39%) were affected by CNVs, with deletion-only, mirror, U-shape, duplication-only models being best fit for 30, 10, 4, 2 phenotypes, respectively, aligning stronger deleteriousness deletion. Upon individually adjusting CNV effects either body mass index (BMI), height, or educational attainment (EA), found that sixteen testable deletion-driven associations-primarily cardiovascular metabolic traits-were BMI dependent, EA playing more subtle role no depending on height. Bidirectional Mendelian randomization supported 13 out these 16 associations secondary consequences CNV's impact BMI. For 23 remained significantly associated upon individual adjustment mediators, matched-control analyses 10 including musculoskeletal traits, liver enzymes, fluid intelligence, platelet count, pneumonia acute kidney injury risk, under strict Bonferroni correction, additional nominally significant associations. These results paint picture BP4-5's pattern involves direct multiple physiological systems indirect co-morbidities consequential EA, acting through trait-specific mechanisms.

Language: Английский

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Sarcopenia and immune-mediated inflammatory diseases: Evaluating causality and exploring therapeutic targets for sarcopenia through Mendelian randomization

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 144, P. 113687 - 113687

Published: Nov. 26, 2024

Language: Английский

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Is exposure to pesticides associated with biological aging? A systematic review and meta-analysis

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102390 - 102390

Published: June 24, 2024

Exposure to pesticides is a risk factor for various diseases, yet its association with biological aging remains unclear. We aimed systematically investigate the relationship between pesticide exposure and aging. PubMed, Embase Web of Science were searched from inception August 2023. Observational studies investigating biomarkers included. Three-level random-effect meta-analysis was used synthesize data. Risk bias assessed by Newcastle-Ottawa Scale. Twenty evaluating associations in 10,368 individuals Sixteen reported telomere length four epigenetic clocks. Meta-analysis showed no statistically significant Hannum clock (pooled β = 0.27; 95%CI: -0.25, 0.79), or Hedges'g -0.46; -1.10, 0.19). However, opposite direction effect two outcomes an indication possible accelerated After removal influential sizes low-quality studies, shorter found higher-exposed populations. The existing evidence limited due scarcity on clocks substantial heterogeneity across examining length. High-quality incorporating more aging, focusing active chemical ingredients accounting potential confounders are needed enhance our understanding impact

Language: Английский

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Pharmacological Manipulation of the Aging Pathways to Effect Health Span and Lifespan with Special Reference to SGLT2 Inhibitors as Powerful Anti-aging Agents in Humans

Insights in Biology and Medicine, Journal Year: 2024, Volume and Issue: 8(1), P. 011 - 025

Published: Oct. 30, 2024

Calorie restriction has been shown to slow the aging process in numerous organisms including primates. Caloric excess states, such as type 2 diabetes, are associated with accelerated and incidence severity of chronic diseases. The nutrient-sensing pathways intestinal microbiome important systems that affect disease development. This manuscript reviews various involved development examines pharmacological manipulation these which appear diseases experimental model collaborating human data when available. Finally, abundance suggesting newer diabetic medications, sodium-glucose transport inhibitors, potent anti-aging agents is provided.

Language: Английский

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