Damaging the Biology of Mice to Make them Age More Rapidly Often Tells Us Little of Use
Posted: August 25, 2013 at 2:53 am
Aging is damage: it is the accumulation of broken and obstructed protein machinery and nanoscale structures inside and around our cells. Living beings come with many varied repair systems, so the processes by which damage grows and eventually overwhelms those repair systems is far from straightforward. In that sense aging isn't like the wearing of stone by the weather, or the failure of a non-repairing mechanical system like a car - but it's still all about damage. At the highest level the same mathematical models of damage and component loss that work just fine as aids to understanding failure in complex non-repairing systems like electronics also work just fine for aging.
Every so often a research group feels the need to publicize work in which they damage mice or other laboratory species in ways that cause them to live shorter lives. There are many very subtle ways to alter genes, such as those involved in DNA repair, that produce what is arguably accelerated aging. (Though not everyone thinks that these forms of life span reduction are in fact accelerated aging, but that's a debate for another time and place). The point here is that I think you have to beware of taking it at face value that these research results are relevant to normal aging, or relevant to extending healthy life. You can damage mice with a hammer if you so choose, and it will certainly shorten their life spans, but examining the results won't tell you anything about aging. Similarly, it's the case that near all of the possible ways of interfering in mouse biology via genes and metabolic operation in order to reduce life span are just as irrelevant.
Here is an example of this sort of thing: researchers are producing mice with additional damage in their mitochondria, a component of cellular biology known to be important in all sorts of metabolic processes, and considered to be important in aging, and showing that these mice don't live as long. I don't think that the authors can show that they've proved much of relevance to aging with this study as constructed, however, for the reasons noted above.
Mutations of mitochondrial DNA can hasten offspring's ageing process
In ageing research, mitochondria have been scrutinized by researchers for a long time already. The mitochondria in a cell contain thousand of copies of a circular DNA genome. These encode, for instance, proteins that are important for the enzymes of the respiratory chain. Whereas the DNA within the nucleus comes from both parents, the mitochondrial DNA (mtDNA) only includes maternal genes, as mitochondria are transmitted to offspring via the oocyte and not via sperm cells. As the numerous DNA molecules within a cell's mitochondria mutate independently from each other, normal and damaged mtDNA molecules are passed to the next generation.
To examine which effects mtDNA damage exerts on offspring, researchers used a mouse model. Mice that inherited mutations of mtDNA from their mother not only died quicker compared to those without inherited defects, but also showed premature ageing effects like reduced body mass or a decrease in male's fertility. Moreover, these rodents were prone to heart muscle disease.
As the researchers discovered, mutations of mtDNA not only can accelerate ageing but also impair development: In mice that, in addition to their inherited defects, accumulated mutations of mtDNA during their lifetime, researchers found disturbances of brain development. They conclude that defects of mtDNA that are inherited and those that are acquired later in life add up and finally reach a critical number.
To show relevance, you really need to demonstrate life extension - meaning repair mechanisms for mitochondrial DNA rather than damage mechanisms should be the focus. To shorten life spans through various forms of damage is unlikely to provide anything more than hints and inference when it comes to ways to extend life.
- Grand Traverse Co. Health Department Seeks Volunteers for Hagerty Center Vaccination Clinics - 9&10 News - January 20th, 2021
- 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
- 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
- Mitochondrial Functional Mutations and Worm Longevity - 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