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Time to highlight the role of Mitochondria in aging
ymedan
Posts: 127 ✭✭✭
https://eurekalert.org/pub_releases/2019-04/mgh-mpp040319.php
Mitochondrial permeability plays a key role in aging, recovery from ischemic injury , recent research from MGH Genomic Center
Mitochondrial permeability plays a key role in aging, recovery from ischemic injury , recent research from MGH Genomic Center
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In mice, eliminating damaged mitochondria alleviates chronic inflammatory disease
Treatment with a choline kinase inhibitor prompts immune cells to clear away damaged mitochondria, thus reducing NLRP3 inflammasome activation and preventing inflammation
UNIVERSITY OF CALIFORNIA - SAN DIEGO
There is an emerging role that mitochondria play in inflammation; how dysregulation of mitochondrial quality control and age-related mitochondrial dysfunction contributes to aging, age-related mitochondrial dysfunction, and the notion of retrograde signalling; and why a little mitochondrial stress might ultimately be a good thing.
Sources: https://www.jci.org/articles/view/120842
I plan on reaching out to Arnon Blum (one of the authors) for comments and discussion.
The causal role of oxidative damage in the aging process is the absence of a clear correlation between the efficacy of antioxidant defences and longevity.
To reach to Arnon Blum, the correspondence address is as hereunder for ready reference:
Toren Finkel, Aging Institute, 100 Technology Drive, Room 555, Pittsburgh, Pennsylvania 15219, USA
Phone: 412.383.4409
Email: finkelt@pitt.edu
Hope you find this useful.
You may find these papers super interesting too.
Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging
https://www.ncbi.nlm.nih.gov/pubmed/28188102
Mammalian Mitochondria and Aging: An Update
https://www.ncbi.nlm.nih.gov/pubmed/28094012
Inflammation and frailty in the elderly: A systematic review and meta-analysis
https://www.ncbi.nlm.nih.gov/pubmed/27592340
Thank you.
Reaching Arnon Blum is much simpler
Since you are into it, you may want to track Minovia
Mitochondrial genetic medicine.
Wallace DC.
Abstract
Inherited mitochondrial DNA (mtDNA) diseases were discovered 30 years ago, and their characterization has provided a new perspective on the etiology of the common metabolic and degenerative diseases, cancer, and aging. The maternally inherited mtDNA contains 37 critical bioenergetic genes that are present in hundreds of copies per cell, but the 'mitochondrial genome' encompasses an additional 1,000-2,000 nuclear DNA (nDNA) mitochondrial genes. The interaction between these two mitochondrial genetic systems provides explanations for phenomena such as the non-Mendelian transmission of the common 'complex' diseases, age-related disease risk and progression, variable penetrance and expressivity, and gene-environment interactions. Thus, mtDNA genetics contributes to the quantitative and environmental components of human genetics that cannot be explained by Mendelian genetics. Because mtDNA is maternally inherited and cytoplasmic, it has fostered the first germline gene therapy, nuclear transplantation. However, effective interventions are still lacking for existing patients with mitochondrial dysfunction.
PMID: 30374071 DOI: 10.1038/s41588-018-0264-z
Microbiota–mitochondria inter-talk: consequence for microbiota–host interaction
Yann Saint-Georges-Chaumet Marvin Edeas
Pathogens and Disease, Volume 74, Issue 1, February 2016, ftv096, https://doi.org/10.1093/femspd/ftv096
In a new study, a University of Missouri scientist suggests a model where mitochondria, or small energy producing parts of cells, could form the basis of what links a person's general intelligence, health and aging. This insight could provide valuable information to researchers studying various genetic and environmental influences and alternative therapies for age-related diseases, such as Alzheimer's disease.
Pre/Pro-biotics is OUT, Pre/Pro-mitochondria is IN :-)
Mitochondria, the 'batteries' that produce our energy, interact with the cell's nucleus in subtle ways previously unseen in humans, according to research published today in the journal Science by University of Cambridge researchers.
@davidsinclair Note the role of Mitochondria in this newly discovered metabolic pathway.
@marz62
NRG Therapeutics is a new UK-based biotech developing novel drugs acting through preservation of mitochondrial function, targeting degenerative diseases such as Parkinson’s, Alzheimer’s disease and motor neuron disease.
Changes in the gut microbiota and the mitochondrial genome are both linked with the development of disease.
Tal Yardeni et al
To investigate why, we examined the gut microbiota of mice harboring various mutations in genes that alter mitochondrial function. These studies revealed that mitochondrial genetic variations altered the composition of the gut microbiota community. In cross-fostering studies, we found that although the initial microbiota community of newborn mice was that obtained from the nursing mother, the microbiota community progressed toward that characteristic of the microbiome of unfostered pups of the same genotype within 2 months. Analysis of the mito-
chondrial DNA variants associated with altered gut microbiota suggested that microbiome species diversity correlated with host reactive oxygen species (ROS) production. To determine whether the abundance of ROS could alter the gut microbiota, mice were aged, treated with N-acetylcysteine, or engineered to express the ROS scavenger catalase specifically within the mitochondria. All three conditions altered the microbiota from that initially established. Thus, these data suggest that
the mitochondrial genotype modulates both ROS production and the species diversity of the gut microbiome, implying that the connection between the gut microbiome and
common disease phenotypes might be due to underlying changes in mitochondrial function.
Here's another thought (though I'm not sure how it fits or if it's of value): It was Lynn Margulis - in her theory of symbiogenesis -- that hypothesized that the mitochondria were originally 'foreign' microbes (with their own intact genomes) that were 'absorbed' or incorporated by a newly evolving single cell life form (perhaps an archaea or proto-bacter micro-organism) whose additional functionality thus contributed to the fitness of the newer, single celled creature, thus guaranteeing its continued presence within the new species (perhaps after co-opting of its key genes by the new host microbe).
I find the connection between the mitochondria of the microbiota and the host cells (intestinal epithelium) quite intriguing; ROS production seems to be a response by the HOST cells to certain bacterial mitochondrial (gene) alterations, etc. There is clearly some type of feedback (or maybe simple cause and effect) going on here, perhaps even an extended form of symbiosis (resembling a type of "pruning" of the microbiota, by host cells, towards the preferred microbiomic genotype).
I await more research.
The reason I started to probe into it was the realization the mDNA has no Telomeres and thus is prone to errors/mutations much more than the host DNA.
I think that we are witnessing a new field of Bio-Archeology in the making
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934418/
Understanding the relationship between estrogen and mitochondria might, therefore, provide better insights into the female aging process.
More and more, I am beginning to consider the role of circadian genes (CLOCK and BMAL1), and their Transcription Factors, in cellular aging (through transcriptional-translational negative feedback loops). These circadian 'clocks' are predominantly located in the SCN of the hypothalamus.
Breakdowns in metabolism (locally controlled by mitochondria), cell signalling and protein folding (and degradation) -- all signs/symptoms of aging -- all seem to be regulated by circadian clocks.
Additionally, glial cells known as astrocytes (for their star-shaped morphology) -- which release the neurotransmitter glutamate -- have been shown to 'rescue' (and lengthen) the periodicity (the rhythmic activity) of dysfunctional cellular "circadia" [M. Brancaccio, et al, 2019*] -- even in the absence of neuronal inputs -- caused by both mutations or (experimental) ablations of the circadian ("sub") genes Cry and Per .
This raises the intriguing possibility (my theory, not expressed by the researchers) that by engineering astrocytes to express circadian rhythmic-activity-lengthening factors (i.e., to SLOW the circadian rhythms that control cellular activity), we might thereby prolong cell life span (thus organismic lifespan).
And yes, environmental input in the form of sunlight (and darkness) plays a key role here (naturally) too...but which could be subsumed via bio-engineering.
*Brancaccio et al - https://science.sciencemag.org/content/363/6423/187