Mitochondrial Functional Mutations and Worm Longevity
Posted: April 21, 2013 at 2:57 am
Many longevity mutations discovered in lower animals such as nematodes involve alterations to mitochondrial function - which only reinforces the apparent importance of mitochondria in determining life span. Mitochondria swarm within cells, working to produce the chemical energy stores used to power cellular operations. In doing so they emit reactive oxygen species, however, that can cause all sorts of harm to the molecular machinery of a cell if not neutralized by a cell's native antioxidants. It is damage to mitochondrial DNA, however, that seems to be one of the root causes of degenerative aging, via a Rube Goldberg sequence of consequences that causes cells to become dysfunctional mass exporters of reactive, harmful molecules.
From a practical therapy standpoint, the research community should be working on ways to repair, replace, or back up mitochondrial DNA in our cells if we want this contribution to aging to go away. That work is very poorly funded, however, in comparison to the benefits it might deliver. Meanwhile, examination of longevity mutations in lower animals continues to reinforce the fact that this is an important direction for therapies to treat and reverse aging.
Some mitochondrial longevity mutations work via hormesis; they cause a slight increase in the level of emitted reactive oxygen species, which in turn causes the cell to react with increased housekeeping and repair activities, resulting in a net gain - less damage over the long term translates into slower aging. Other mutations lower the level of emitted reactive oxygen species, which again means less damage over the long term. Yet more mitochondrial mutations extend life in less obvious ways, or cause mitochondrial dysfunction that appears at the high level to be broadly similar to that of longevity mutants, yet reduces life span. Once you start digging in to the mechanisms of the mitochondrial interior - the electron transport chain with it's multiple complexes - it's all far from simple
Here is an example of research into the mechanisms of mitochondrial longevity mutations in nematode worms:
Many Caenorhabditis elegans mutants with dysfunctional mitochondrial electron transport chain are surprisingly long lived. Both short-lived (gas-1(fc21)) and long-lived (nuo-6(qm200)) mutants of mitochondrial complex I have been identified. However, it is not clear what are the pathways determining the difference in longevity.
We show that even in a short-lived gas-1(fc21) mutant, many longevity assurance pathways, shown to be important for lifespan prolongation in long-lived mutants, are active. Beside similar dependence on alternative metabolic pathways, short-lived gas-1(fc21) mutants and long-lived nuo-6(qm200) mutants also activate hypoxia-inducible factor-1? (HIF-1?) stress pathway and mitochondrial unfolded protein response (UPRmt).
The major difference that we detected between mutants of different longevity is in the massive loss of complex I accompanied by upregulation of complex II levels, only in short-lived, gas-1(fc21) mutant. We show that high levels of complex II negatively regulate longevity in gas-1(fc21) mutant by decreasing the stability of complex I. Furthermore, our results demonstrate that increase in complex I stability, improves mitochondrial function and decreases mitochondrial stress, putting it inside a "window" of mitochondrial dysfunction that allows lifespan prolongation.
Link: http://dx.doi.org/10.1371/journal.pone.0059493
Source:
http://www.fightaging.org/archives/2013/04/mitochondrial-functional-mutations-and-worm-longevity.php
- How to live longer: Should you skip breakfast to promote longevity? Doctor weighs in - Express - December 28th, 2020
- China Long Avoided Talking About Mental Health. Then Covid Hit. - The New York Times - December 22nd, 2020
- With fitness centers shut down due to COVID-19, home gyms are on the rise - SW News Media - December 10th, 2020
- Review: Equinox Takes Luxe Fitness Into The Wild at Their First Outdoor Gym in LA - InsideHook - September 30th, 2020
- Colorados fitness industry starting to reawaken, but some studios will never reopen - Loveland Reporter-Herald - June 16th, 2020
- In sickness and in health: North Spokane couple weds in front yard during pandemic - The Spokesman-Review - May 18th, 2020
- Furry Friends Provide Big Benefits - June 20th, 2018
- CT Nutrition Consultants - Registered Dietitian - July 12th, 2017
- Channel Update - Fitness & Football Videos Only! - Video - August 10th, 2014
- Measuring the Impact of Cytomegalovirus in Younger People - September 1st, 2013
- Decreased mTOR Expression Provides 20% Mean Life Span Extension in Mice - September 1st, 2013
- A Collagen Patch to Spur Heart Tissue Repair - September 1st, 2013
- Statin Use Correlates With Higher Telomerase Activity - September 1st, 2013
- Children of Long-Lived Parents Have Better Immune Systems - September 1st, 2013
- A Two-Part Report on Global Futures 2045 - August 25th, 2013
- The Next Few Years of Research Into Alzheimer's Disease - August 25th, 2013
- A Look Back at Some of the Roots of Modern Thought on Radical Life Extension - August 25th, 2013
- Damaging the Biology of Mice to Make them Age More Rapidly Often Tells Us Little of Use - August 25th, 2013
- Calorie Restriction as a Means to Augment Cancer Therapies - August 25th, 2013
- Life Without Ageing: Aubrey de Grey and Tom Kirkwood to Debate Longevity Science at the British Science Festival - August 18th, 2013
- A Short Overview of 3-D Printing in Tissue Engineering - August 18th, 2013
- Another Way to Improve Memory in Old Mice - August 18th, 2013
- SENS Research Foundation Releases 2013 Research Report - August 18th, 2013
- Targeting Redox Biology to Reverse Mitochondrial Dysfunction - August 18th, 2013
- The Cost of Living Longer, Even in Good Health - August 11th, 2013
- Signs of Progress: Insurers Talk of Radical Life Extension - August 11th, 2013
- The Current State of Knowledge of Genetics and Longevity - August 11th, 2013
- A Video Tour of Alcor and Interview With Max More - August 11th, 2013
- And Now For Something Reprehensible - August 11th, 2013
- Opposing the Argument that Increased Longevity Will Slow Progress, and is Therefore Undesirable - August 4th, 2013
- Considering State Opposition to Life Extension Technologies - August 4th, 2013
- Steps Towards a Tissue Engineered Thymus - August 4th, 2013
- The Intersection of Kickstarter-Style Fundraising for Research and Distributed Development in Complex Problems - August 4th, 2013
- The Cost of Being Tall is a Shorter Life Expectancy - August 4th, 2013
- A Little Methionine Restriction Research - June 16th, 2013
- Calorie Restriction Versus Resveratrol Treatment - June 16th, 2013
- Reviewing the Literature on Calorie Restriction and Oxidative Stress - June 16th, 2013
- Arguing By Induction For an Absence of Boredom in an Ageless, Greatly Extended Healthy Life - June 16th, 2013
- Investigating Fingertip Regeneration in Mammals - June 16th, 2013
- The Incentives Associated With Becoming a Machine Entity - June 9th, 2013
- A Good Scientific Polemic on Aging - June 9th, 2013
- Quantifying Neurogenesis in Adult Humans - June 9th, 2013
- Considering the Details of Replacing the Brain - June 9th, 2013
- Overreacting in the Direction of Doing Nothing - June 9th, 2013
- Considering the Regenerative Signals Emitted by Transplanted Stem Cells - June 2nd, 2013
- A Bioprosthetic Heart - June 2nd, 2013
- Exercise Versus Peripheral Artery Disease - June 2nd, 2013
- Bracketed by Billionaires - June 2nd, 2013
- Stem Cell Transplants for Leukemia Showing Improved Outcomes - June 2nd, 2013
- Videos from the SENS Research Foundation Evidence Studios Event in December 2012 - May 26th, 2013
- Early Mortality Rates Predict Late Mortality Rates - May 26th, 2013
- Decellularization May Enable Use of More Donor Organs - May 26th, 2013
- Mitochondrially Targeted Antioxidant SS-31 Reverses Some Measures of Aging in Muscle - May 26th, 2013
- Arguing for the Role of Nuclear DNA Damage in Aging - May 26th, 2013
- Reviewing the Results of Calorie Restriction Primate Studies - May 19th, 2013
- A Possible Biomarker for Senescent Cells - May 19th, 2013
- Inhibiting ICMT as a Progeria Therapy - May 19th, 2013
- Are the Most Influential Futurists Those Who Put in the Work to Make Their Visions Real? - May 19th, 2013
- Excess Body Fat Hardens Arteries - May 19th, 2013
- Comments on Rapamycin and Metformin - May 12th, 2013
- The Present State of Artificial Retinas - May 12th, 2013
- The State of Electromechanical and Bioartifical Organs - May 12th, 2013
- Parabiosis Points to GDF-11 as a Means to Reverse Age-Related Cardiac Hypertrophy - May 12th, 2013
- Insights into Inflammaging - May 12th, 2013
- A Different Take on NF-?B and the Hypothalamus - May 5th, 2013
- T-Regulatory Cells More Numerous in the Aged Immune System - May 5th, 2013
- HMGA1 as a Potential Common Mechanism in Cancer - May 5th, 2013
- Recent Research Results from the Study of Naked Mole Rats - May 5th, 2013
- A Skeptical View of Mitochondrial DNA Damage and Aging - May 5th, 2013
- Recent Calorie Restriction Research - April 28th, 2013
- Joining the Dots in Genetic Parkinson's Disease - April 28th, 2013
- Considering the Electron Transport Chain in Aging - April 28th, 2013
- More Data on Granulocyte Transplant Cancer Therapies - April 28th, 2013
- Measures of Mitochondrial DNA Damage Lower in Long-Lived Mice - April 28th, 2013
- Aubrey de Grey on "The Undoing of Aging" - April 21st, 2013
- Indy Mutations and Fly Longevity - April 21st, 2013
- Further Research on BubR1, Cellular Senescence, and Aging - April 21st, 2013
- Sterilized Dogs Live Longer - April 21st, 2013
- Robust Cancer Therapies Will Mean a Greater Use of Aggressive Stem Cell Therapies - April 14th, 2013
- Limited Evidence for the Universality of Heat Shock Hormesis as a Way to Induce Longevity - April 14th, 2013