Combined Impact of Telomere Length and Mitochondrial DNA Copy Number on Cognitive Function in Community-Dwelling Very Old Adults

2017 ◽  
Vol 44 (3-4) ◽  
pp. 232-243 ◽  
Author(s):  
Jee-Yon Lee ◽  
Jung-Ha Kim ◽  
Duk-Chul Lee
Keyword(s):  
Mitochondrial Dna ◽  
Cognitive Function ◽  
Telomere Length ◽  
Odds Ratio ◽  
Copy Number ◽  
Adjusted Odds Ratio ◽  
Community Dwelling ◽  
Mtdna Copy Number ◽  
Old Adults ◽  
Combined Impact

Background: This study was conducted to investigate the combined impact of telomere length and mitochondrial DNA (mtDNA) copy number on cognitive function in community-dwelling very old adults. Methods: In total, 186 subjects over 75 years participated in this study. Cognitive function was assessed using the Korean Mini-Mental State Examination, and leukocyte telomere length and mtDNA copy number were measured using real-time polymerase chain reaction methods. Results: Both the fourth quartile of telomere length and mtDNA copy number were associated with cognitive dysfunction with an adjusted odds ratio of 0.23 (95% confidence interval (CI), 0.10-0.75) and 0.18 (95% CI, 0.03-0.54), respectively. Participants in the high telomere length/high mtDNA copy number group were more likely to have cognitive dysfunction than participants in the low telomere/low mtDNA copy number group with an adjusted odds ratio of 0.19 (95% CI, 0.07-0.58). Conclusion: Our results collectively suggest that the combination of telomere length and mtDNA copy number may be useful for monitoring cognitive decline in older adults.

scholarly journals Mitochondrial Biogenesis, Telomere Length and Cellular Senescence in Parkinson’s Disease and Lewy Body Dementia

2021 ◽  
Author(s):  
Muhammad Asghar ◽  
Amani Odeh ◽  
Ahmad Jouni Fattahi ◽  
Alexandra Edward Henriksson ◽  
Aurelie Miglar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Telomere Length ◽  
Cellular Senescence ◽  
Mitochondrial Biogenesis ◽  
Copy Number ◽  
Cellular Aging ◽  
Mtdna Copy Number

Abstract Background Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during the course of Parkinson’s disease (PD) have been implicated in previous studies, however majority of these studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. Method Here, we have studied the association of PD with three aging hallmarks (telomere attrition, mitochondrial dysfunction, and cellular senescence) in blood and the brain tissue. Telomere length and mitochondrial DNA ( mtDNA ) copy number was assessed by qPCR, while mitochondrial function ( PGC-1α and PGC-1β ) and expression of cyclin-dependent kinase inhibitor 2A ( CDKN2A ), cellular senescence marker was measured by RT-qPCR. Results Our results show that patients diagnosed with PD had 20% lower mitochondrial DNA copy number but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose). Similar results were found in brain tissue, where patients with Parkinson’s disease (PD), Parkinson dementia (PDD) and Dementia with Lewy Bodies (DLB) showed (46-95%) depleted mtDNA copy number, but (7-9%) longer telomeres compared to controls. Furthermore, when compared to controls, patients had lower mitochondrial biogenesis ( PGC-1α and PGC-1β ) and higher load of cellular senescent cells in postmortem prefrontal cortex tissue, where DLB showing the highest effect among the patient groups. Conclusion Our results show that mitochondrial dysfunction and cellular senescence but not telomere shortening is associated with PD, PDD and DLB. Our findings suggest that mitochondrial copy number and function could be used as viable biomarker in blood as an early indicator for the risk of neurodegenerative diseases.

Loss of the Association between Telomere Length and Mitochondrial DNA Copy Number Contribute to Colorectal Carcinogenesis

2017 ◽  
Vol 24 (2) ◽  
pp. 323-328 ◽  
Author(s):  
Hyunsu Lee ◽  
Ji-Hyoung Cho ◽  
Won-Jin Park ◽  
Soo-Jung Jung ◽  
In-Jang Choi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Telomere Length ◽  
Copy Number ◽  
Colorectal Carcinogenesis ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

scholarly journals Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer

2017 ◽  
Vol 14 (1) ◽  
pp. 925-929 ◽  
Author(s):  
Soo-Jung Jung ◽  
Ji-Hyoung Cho ◽  
Won-Jin Park ◽  
Yu-Ran Heo ◽  
Jae-Ho Lee
Keyword(s):  
Gastric Cancer ◽  
Mitochondrial Dna ◽  
Telomere Length ◽  
Copy Number ◽  
Diffuse Gastric Cancer ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

scholarly journals mtDNA in the Pathogenesis of Cardiovascular Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Lili Wang ◽  
Qianhui Zhang ◽  
Kexin Yuan ◽  
Jing Yuan
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Heart Diseases ◽  
Mtdna Copy Number ◽  
Cardiac Inflammation ◽  
Ischemic Heart Diseases ◽  
Metabolic Functions ◽  
Underlying Mechanisms

The incidence rate of cardiovascular disease (CVD) has been increasing year by year and has become the main cause for the increase of mortality. Mitochondrial DNA (mtDNA) plays a crucial role in the pathogenesis of CVD, especially in heart failure and ischemic heart diseases. With the deepening of research, more and more evidence showed that mtDNA is related to the occurrence and development of CVD. Current studies mainly focus on how mtDNA copy number, an indirect biomarker of mitochondrial function, contributes to CVD and its underlying mechanisms including mtDNA autophagy, the effect of mtDNA on cardiac inflammation, and related metabolic functions. However, no relevant studies have been conducted yet. In this paper, we combed the current research status of the mechanism related to the influence of mtDNA on the occurrence, development, and prognosis of CVD, so as to find whether these mechanisms have something in common, or is there a correlation between each mechanism for the development of CVD?

scholarly journals Born to be young: prenatal thyroid hormones increase early-life telomere length

2020 ◽  
Author(s):  
Antoine Stier ◽  
Bin-Yan Hsu ◽  
Coline Marciau ◽  
Blandine Doligez ◽  
Lars Gustafsson ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Telomere Length ◽  
Early Life ◽  
Copy Number ◽  
Growth Period ◽  
Postnatal Growth ◽  
Mtdna Copy Number ◽  
Underlying Mechanisms ◽  
Growth And Aging ◽  
Positive Effect

AbstractPrenatal environmental conditions can have lifelong consequences on health and aging. The underlying mechanisms remain nonetheless little understood. Thyroid hormones (THs) are important regulators of embryogenesis transferred from the mother to the embryo. In an avian model, we manipulated embryo exposure to maternal THs through egg injection and investigated the consequences on postnatal growth and aging. We first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus confirming that these two molecular markers are hallmarks of aging in our wild bird model. The experimental elevation of prenatal THs levels had a transient positive effect on postnatal growth. Elevated prenatal THs had no effect on mtDNA copy number but significantly increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca. 4 years of post-growth telomere shortening). These findings suggest that prenatal THs have a key role in setting the ‘biological’ age at birth, and thus might influence longevity.

scholarly journals Telomere length and cognitive function in southern Chinese community-dwelling male elders

2013 ◽  
Vol 42 (4) ◽  
pp. 450-455 ◽  
Author(s):  
S. L. Ma ◽  
E. S. S. Lau ◽  
E. W. C. Suen ◽  
L. C. W. Lam ◽  
P. C. Leung ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Telomere Length ◽  
Community Dwelling ◽  
Chinese Community ◽  
Southern Chinese

scholarly journals Targeting reduced mitochondrial DNA quantity as a therapeutic approach in pediatric high-grade gliomas

2019 ◽  
Vol 22 (1) ◽  
pp. 139-151 ◽  
Author(s):  
Han Shen ◽  
Man Yu ◽  
Maria Tsoli ◽  
Cecilia Chang ◽  
Swapna Joshi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Glucose Metabolism ◽  
Mitochondrial Function ◽  
Copy Number ◽  
Pyruvate Dehydrogenase Kinase ◽  
High Grade ◽  
Mtdna Copy Number ◽  
Mitochondrial Oxidation ◽  
High Grade Gliomas

Abstract Background Despite increased understanding of the genetic events underlying pediatric high-grade gliomas (pHGGs), therapeutic progress is static, with poor understanding of nongenomic drivers. We therefore investigated the role of alterations in mitochondrial function and developed an effective combination therapy against pHGGs. Methods Mitochondrial DNA (mtDNA) copy number was measured in a cohort of 60 pHGGs. The implication of mtDNA alteration in pHGG tumorigenesis was studied and followed by an efficacy investigation using patient-derived cultures and orthotopic xenografts. Results Average mtDNA content was significantly lower in tumors versus normal brains. Decreasing mtDNA copy number in normal human astrocytes led to a markedly increased tumorigenicity in vivo. Depletion of mtDNA in pHGG cells promoted cell migration and invasion and therapeutic resistance. Shifting glucose metabolism from glycolysis to mitochondrial oxidation with the adenosine monophosphate–activated protein kinase activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) or the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA) significantly inhibited pHGG viability. Using DCA to shift glucose metabolism to mitochondrial oxidation and then metformin to simultaneously target mitochondrial function disrupted energy homeostasis of tumor cells, increasing DNA damage and apoptosis. The triple combination with radiation therapy, DCA and metformin led to a more potent therapeutic effect in vitro and in vivo. Conclusions Our results suggest metabolic alterations as an onco-requisite factor of pHGG tumorigenesis. Targeting reduced mtDNA quantity represents a promising therapeutic strategy for pHGG.

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