Publications by authors named "Vilhelm Bohr"
Dysfunctional mitophagy is a key component of Alzheimer's disease (AD) pathology, yet direct evidence and mechanistic insights remain limited. Using a mitophagy reporter in an AD mouse model ( / /mt-Keima), we identified mitochondrial plaques (MPs) composed of accumulated mitochondria within or outside lysosomes in AD, but not normal mouse brains. Similar structures were also found in AD human brains, but not in healthy controls.
View Article and Find Full Text PDFRecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).
View Article and Find Full Text PDFAlzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.
View Article and Find Full Text PDFIntroduction: During aging, many cellular processes, such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses, become compromised. Urolithin A (UA) and Nicotinamide Riboside (NR) are two naturally occurring compounds known for their anti-inflammatory and mitochondrial protective properties, yet the effects of these natural substances on microglia cells have not been thoroughly investigated. As both UA and NR are considered safe dietary supplements, it is equally important to understand their function in normal cells and in disease states.
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- * Results show that centenarians with better physical capabilities have more mtDNA and lower mitochondrial dysfunction compared to those with disabilities.
- * Additionally, correlations were found between grip strength, mtDNA copy number, and DNA repair enzyme activity, indicating that maintaining mitochondrial function might help preserve physical abilities in very old age.
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- * The study investigated NR's effects using various models that simulate oxidative stress, aging, and AD, focusing on neuronal survival and the complex interactions of reactive species.
- * Findings reveal that NR treatment affects specific protein networks related to energy metabolism and neurotransmitter regulation, suggesting potential pathways for modifying the disease processes in AD.
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- FOXO transcription factors influence aging and longevity by regulating specific target genes, one of which is OSER1, a gene that extends lifespan in various species like silkworms, nematodes, and flies when overexpressed.* -
- Overexpression of OSER1 enhances resistance to oxidative stress, starvation, and heat shock in flies, while its depletion increases vulnerability to these stressors and shortens lifespan; similar effects are observed in C. elegans and silkworms.* -
- OSER1 is linked to important biological processes such as oxidative stress response and mitochondrial health, suggesting that it may play a role in healthy aging and even human longevity, as indicated by genetic studies.*
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- Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by the buildup of amyloid plaques and tau tangles, leading to memory loss and brain damage.
- Researchers used a C. elegans model to explore the role of DNA glycosylases in AD progression, discovering that certain genetic modifications improved mitochondrial health, lifespan, and cognitive function in nematodes with tau pathology.
- The study highlights the importance of the DNA glycosylase NTH-1, showing it has additional functions beyond its enzyme activity, suggesting it could be a potential target for therapeutic strategies against tau-related diseases.
Article Synopsis
- * In fibroblasts from patients with sporadic Alzheimer's disease (sAD), researchers found increased mitochondrial reactive oxygen species (ROS), altered mitochondrial function, and defects in degradation pathways compared to healthy controls.
- * While lysosome levels were high in sAD fibroblasts, their ability to degrade was impaired; additionally, nicotinamide riboside supplementation reduced mitochondrial ROS but did not improve lysosomal function.
Article Synopsis
- - Urolithin A (UA), a compound derived from ellagic acid, shows promise in improving cognitive functions and countering amyloid beta and tau pathologies in Alzheimer's disease (AD) models in mice.
- - Long-term UA treatment enhances mitophagy by boosting lysosomal functions and normalizing lysosomal cathepsins, especially cathepsin Z, which is crucial for its therapeutic effects on AD.
- - The findings underscore the significance of lysosomal dysfunction in AD and suggest UA as a potential treatment by influencing immune responses and AD-related pathways.
Article Synopsis
- Researchers are investigating the link between sensory deficiencies, particularly hearing loss, and the development of Alzheimer's disease (AD), which remains poorly understood.
- In a study with two AD mouse models, early-onset hearing loss was found to occur at a young age, before any cognitive changes, indicating that hearing impairment may be an early sign of AD.
- The study suggests that DNA damage in the cochlea could be a contributing factor to this hearing dysfunction in AD, as evidenced by specific markers indicating mitochondrial impairment and reduced synaptic function in auditory cells.
Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations.
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- - Ataxia with oculomotor apraxia type 1 (AOA1) is a neurodegenerative disorder that leads to coordination issues in movement, speech, and eye tracking, caused by mutations in the APTX gene which is important for DNA repair.
- - APTX deficiency results in mitochondrial dysfunction and increased DNA damage, which may activate immune responses, leading to inflammation due to misplacement of DNA in the cells.
- - The study found that APTX knockout in microglial cells affects their immune response, with downregulation of key pathways related to DNA and RNA sensing, suggesting the need for further research into potential treatments for AOA1.
Article Synopsis
- NAD is a crucial metabolite involved in various cellular functions like metabolism, energy production, DNA repair, and inflammation, with research showing its levels decline with aging and related diseases.
- The text outlines the discovery of NAD and how its production and consumption pathways may impact aging and neurodegenerative diseases due to imbalances.
- Preclinical studies indicate that NAD precursors could promote healthy aging and treat conditions like Alzheimer's and Parkinson's, leading to ongoing clinical trials to explore their clinical potential and understand aging mechanisms better.
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- * Salidroside (SA), a natural compound from Rhodiola rosea, was found to prolong lifespan and show anti-aging and antioxidative effects.
- * SA works by binding to heat shock protein 90 (HSP90) and inhibiting its ATPase activity, which influences protein interactions and gene expression related to aging and oxidative stress.
Article Synopsis
- Replication stress from a deficiency leads to mitochondrial dysfunction and metabolic stress, causing significant changes in metabolites.
- Supplementation with NAD and its precursor, nicotinamide riboside (NR), can restore autophagy and improve mitochondrial morphology in mouse embryonic fibroblasts (MEFs).
- However, while NR supplementation helps MEFs, it does not protect nematodes from oxidative stress caused by the deficiency, indicating variability in intervention effectiveness depending on the organism.
Article Synopsis
- * Nicotinamide Riboside (NR), which is known for its safety and efficacy in other health conditions, has shown promise in preventing the progression of ARHL in mouse models.
- * NR works by restoring crucial NAD+ levels in the cochlea and enhancing biological pathways involved in hearing, while also targeting new mechanisms related to lipid droplet formation in the auditory system.
Article Synopsis
- * The specific type of DNA damage, 8-oxoG, is repaired by OGG1, an enzyme found in the nucleus and mitochondria, playing a crucial role in maintaining mitochondrial function and reducing inflammation.
- * Enhanced expression of mitochondria-targeted OGG1 (mtOGG1) in transgenic mice shows promise in reversing age-related inflammation and improving mitochondrial functions, with notable differences in response between male and female mice.
Article Synopsis
- RecQ helicases are crucial for maintaining DNA stability and are linked to various diseases when dysfunctional, such as cancer and neurodegeneration.
- This study examined the effects of ionizing radiation (IR) on mice lacking specific RecQ proteins (RecQ1, WRN, and RecQ4), revealing abnormal behavior patterns, including social and depressive-like issues.
- Transcriptomic and metabolomic analyses indicated significant changes in neurological pathways and increased DNA damage responses in these mice, highlighting potential therapeutic targets like the Aldob and Nox4 genes.
Article Synopsis
- - Olfactory dysfunction is a common issue in elderly people and can signal neurodegenerative diseases like Alzheimer's and Parkinson's, but it's also found in typical aging, making it crucial to study its roots in non-pathological aging.
- - In a study with C57BL/6J mice, researchers found that the ability to distinguish odors declined the most as mice aged, while general odor detection and sensitivity also decreased, but their ability to get used to smells (habituation) stayed intact.
- - The aging process in mice was linked to increased signs of oxidative stress, inflammation, and DNA damage in the olfactory bulb, while boosting NAD levels showed promise in enhancing their olfactory function and overall health.
Article Synopsis
- Short telomeres are a key characteristic of telomere biology disorders (TBDs) like dyskeratosis congenita (DC), which currently lack effective cures and can lead to bone marrow failure.
- Researchers studied how NAD supplementation, specifically using the precursor nicotinamide riboside (NR), affects health in mice with critically short telomeres.
- Results showed that NR not only improved body weight and telomere integrity but also reduced inflammation and other health issues associated with telomere impairment, hinting at NAD supplementation as a potential treatment option.
Article Synopsis
- Oligomeric state determination of enzymes like RecQ helicases is crucial for understanding their catalytic functions, but there's still uncertainty about how these states relate to their biochemical activities.
- Researchers used single-molecule multi-color fluorescence imaging to study the Werner syndrome protein (WRN) and found it binds as a dimer to forked DNA and remains a dimer while unwinding it, but forms a tetramer at a replication fork and then dimerizes to activate fork regression.
- By selectively inhibiting WRN's helicase function on certain strands, they demonstrated how active dimers of WRN utilize ATP hydrolysis energy for both unwinding and regression tasks.
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- - PARPs are crucial for DNA damage repair, but while we know about nuclear PARP functions, the role of mitochondrial PARP (mtPARP) remains largely unexplored and controversial.
- - This study provides evidence of PARP1 and poly ADP-ribosylation (PARylation) occurring in purified mitochondria, where adding NAD stimulates this process.
- - Results indicate that PARP1 not only participates in mitochondrial PARylation but also plays a role in regulating the transcription of mitochondrial DNA (mtDNA) through NAD-dependent activity.
Effects of lifespan-extending interventions on cognitive healthspan.
Expert Rev Mol Med
November 2022
Article Synopsis
- Ageing is the leading risk factor for neurodegenerative diseases like Alzheimer's and Parkinson's, which are currently incurable and worsen over time.
- This review examines various interventions that may help extend lifespan in animals and their potential effects on cognitive health and neurodegeneration.
- The authors emphasize the need for large-scale, long-term studies to better understand these interventions and their impact on cognitive function, especially in older adults.
Article Synopsis
- Alzheimer's disease (AD) is a leading neurodegenerative condition linked to gut dysbiosis, where the gut microbiota impacts aging and neurodegeneration.
- Previous research showed that nicotinamide riboside (NR), an NAD precursor, helped reduce brain issues related to AD, but its effects on gut microbiota were unclear.
- In this study with APP/PS1 transgenic mice, NR administration restored gut microbiota diversity and composition, highlighting its potential role in addressing gut dysbiosis as part of AD treatment.