Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson’s disease and Lewy body dementia
(2022) In Scientific Reports 12(1).- Abstract
Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during Parkinson’s disease (PD) have been implicated in previous studies, however the majority of studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. 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. Our results show that PD patients had 20% lower mitochondrial DNA copies but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose, LEDD) and disease... (More)
Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during Parkinson’s disease (PD) have been implicated in previous studies, however the majority of studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. 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. Our results show that PD patients had 20% lower mitochondrial DNA copies but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose, LEDD) and disease duration. Similar results were found in brain tissue, where patients with Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and Dementia with Lewy Bodies (DLB) showed (46–95%) depleted mtDNA copies, but (7–9%) longer telomeres compared to controls. In addition, patients had lower mitochondrial biogenesis (PGC-1α and PGC-1β) and higher load of a cellular senescence marker in postmortem prefrontal cortex tissue, with DLB showing the highest effect among the patient groups. Our results suggest that mitochondrial dysfunction (copy number and biogenesis) in blood might be a valuable marker to assess the risk of PD. However, further studies with larger sample size are needed to evaluate these findings.
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- author
- Asghar, Muhammad LU ; Odeh, Amani ; Fattahi, Ahmad Jouni ; Henriksson, Alexandra Edwards ; Miglar, Aurelie ; Khosousi, Shervin and Svenningsson, Per
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 12
- issue
- 1
- article number
- 17578
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85140249001
- pmid:36266468
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-022-22400-z
- language
- English
- LU publication?
- yes
- id
- 4a06d66a-4540-429d-8ec1-ecbb4f1e9e64
- date added to LUP
- 2022-12-06 15:33:57
- date last changed
- 2024-06-15 02:00:35
@article{4a06d66a-4540-429d-8ec1-ecbb4f1e9e64,
abstract = {{<p>Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during Parkinson’s disease (PD) have been implicated in previous studies, however the majority of studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. 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. Our results show that PD patients had 20% lower mitochondrial DNA copies but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose, LEDD) and disease duration. Similar results were found in brain tissue, where patients with Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and Dementia with Lewy Bodies (DLB) showed (46–95%) depleted mtDNA copies, but (7–9%) longer telomeres compared to controls. In addition, patients had lower mitochondrial biogenesis (PGC-1α and PGC-1β) and higher load of a cellular senescence marker in postmortem prefrontal cortex tissue, with DLB showing the highest effect among the patient groups. Our results suggest that mitochondrial dysfunction (copy number and biogenesis) in blood might be a valuable marker to assess the risk of PD. However, further studies with larger sample size are needed to evaluate these findings.</p>}},
author = {{Asghar, Muhammad and Odeh, Amani and Fattahi, Ahmad Jouni and Henriksson, Alexandra Edwards and Miglar, Aurelie and Khosousi, Shervin and Svenningsson, Per}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson’s disease and Lewy body dementia}},
url = {{http://dx.doi.org/10.1038/s41598-022-22400-z}},
doi = {{10.1038/s41598-022-22400-z}},
volume = {{12}},
year = {{2022}},
}