Wednesday, October 28, 2020
Mitochondrial Health

The Hallmarks of Aging: Mitochondrial dysfunction | LifeXtenShow



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Your cells teem with small machinery and devices of all kinds, including teeny tiny batteries called mitochondria. Just like real batteries, they can malfunction, but replacing them isn’t that easy. In this episode, Veera explains what happens to our microbatteries with aging and what we can do about it.

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Music:

Intro jingle courtesy of Kevin MacLeod – Incompetech.com

Salk Institute picture: Jim Harper (https://commons.wikimedia.org/wiki/File:Salk_Institute1.jpg)
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Sources:

Free radicals as signals of stress:
Hekimi S, Lapointe J, Wen Y. Taking a “good” look at free radicals in the aging process. Trends Cell Biol. 2011;21(10):569–576. doi:10.1016/j.tcb.2011.06.008 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074523/)

About the J147 experimental drug:
Joshua Goldberg et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell, 2018 DOI: 10.1111/acel.12715 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847861/)

Physiological role of mitochondrial free radicals:
Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158–167. doi:10.1016/j.molcel.2012.09.025 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484374/)

Studies on urolithin:
Ryu, D., Mouchiroud, L., Andreux, P. et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med 22, 879–888 (2016) doi:10.1038/nm.4132
(https://www.nature.com/articles/nm.4132)

Andreux, P.A., Blanco-Bose, W., Ryu, D. et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab 1, 595–603 (2019) doi:10.1038/s42255-019-0073-4 (https://www.nature.com/articles/s42255-019-0073-4#citeas)

Mitochondrial dysfunction and neuronal dysfunction:

Gibson, G. E., Starkov, A., Blass, J. P., Ratan, R. R., & Beal, M. F. (2010). Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1802(1), 122-134. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790547/)

First allotopic expression study by SENS Research Foundation:

Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100594/)

Pathologies associated with mitochondrial dysfunction:

Cwerman-Thibault, H., Sahel, J. A., & Corral-Debrinski, M. (2011). Mitochondrial medicine: to a new era of gene therapy for mitochondrial DNA mutations. Journal of inherited metabolic disease, 34(2), 327-344.
(https://www.ncbi.nlm.nih.gov/pubmed/20571866)

J147 clinical trial: https://www.lifespan.io/road-maps/salk-institute-j147
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#Mitochondria #Aging #MolecularBiology #SENS #SENSResearchFoundation #AllotopicExpression #MitochondrialGenes #mtDNA #LifeExtension #FreeRadicals

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8 thoughts on “The Hallmarks of Aging: Mitochondrial dysfunction | LifeXtenShow
  1. Another fantastic video, thank you. I remember MitoSENS seeming a bit too ambitious when I first heard about it back in 2010 or so, but it looks like they've made real progress and I can't wait to see how the next phase turns out!

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