Damage to the special DNA in our cells' energy stores is a key cause for getting old and sick with age. Here's what you should know:
- These cell parts make energy but also create bad stuff called reactive oxygen types (ROS), which hurt this special DNA.
- This DNA is easier to hurt than the DNA in the cell center because it doesn’t have strong shields and fix-up ways.
- Bad oxygen from ROS changes this DNA, making less energy, more ROS, and a bad loop of hurt.
- Illnesses like Alzheimer's, Parkinson's, and cancer come from this DNA hurt by bad oxygen.
- Cells try to fix this DNA using a method called Base Cut Repair (BER) or they get rid of very hurt parts through a cleanup process.
- Changes in how you live like moving more, eating things full of antioxidants, and keeping calm can guard this DNA.
- Pills like NMN, Resveratrol, and Spermidine might help these cell parts stay healthy by cutting down bad oxygen and helping in repair.
Quick Look
| Main Point | Info |
|---|---|
| Big Cause of Harm | Bad oxygen types (ROS) from cell power work |
| Age Problem | Makes cell age fast, raises bad changes in mtDNA |
| Fix Way | Base Excision Repair (BER) mends small breaks; mitophagy cuts out bad mitochondria |
| Tied Health Issues | Alzheimer's, Parkinson's, Huntington's, cancer |
| Ways to Stop It | Work out, eat good-for-you stuff, stay away from bad air, know how to chill |
| Good Extra Stuff | NMN, Resveratrol, Spermidine, Fisetin |
Keeping your cell power parts safe is key for good old age health. By mixing life changes and special add-ons, you can cut down on cell harm and keep cell health fine.
DNA Oxidation | DNA Damage by ROS
Main Causes and Kinds of Big Cell Energy Unit Stress
Big Cell Energy Units make oxygen types that react mostly from the power move line, with Units one and three as the big helpers.
Key Spots for Making ROS in Big Cell Power Units
Most of the ROS in cells, about 90%, are made in the Big Cell Energy Units, where the power move line is the main maker. Unit one and Unit three work the most in making ROS when normal energy is made. Unit one sends ROS mostly into the inside of the Big Cell Energy Unit. But, Unit three is different because it makes a kind of oxygen that reacts in two ways - inside and between the layers - making it a key stress spot. Damage to the DNA in Energy Units can make this worse, increasing ROS making. From 0.2% to 2.0% of the air these units use is made into this reactive oxygen, with more enzymes adding to the stress load [3]. These ROS spots play a big part in hurting the DNA in Energy Units, as listed below.
Kinds of Damage to DNA in Energy Units from Stress
Stress affects DNA in energy units through ways like changes in bases, problems in lining up, and breaks in the strand. Single breaks in the strand are bad, but double breaks are worse. ROS can also make sites with no base and breaks in chains, which may lead to lost DNA info. For example, when human cells get 200 μM hydrogen peroxide, about four issues happen for every 10,000 base parts, and even after six hours, fixes are only partly done [2]. When DNA changes in these cells pass 60% to 80%, the work of the energy units drops a lot [2]. These issues in the DNA of energy units not just weaken it but also drive the start of diseases that come with age.
ROS and Diseases that Come with Age
High ROS in these big units and the related damage are closely tied to diseases that come as people get older. For instance, in Alzheimer's disease, less work in a part of the power move line makes it less good [168–170]. In Parkinson's disease, a lot of change in Unit one's work is seen, and things that block Unit one can cause like-Parkinson's signs. The same goes for Huntington's disease, where wrong shapes and working of Energy Units are seen in people and in animal tests. Studies show that ROS marks in DNA in Energy Units are a lot more than in main DNA, growing by up to 15 times in people older than 70 [4]. High levels of ROS also mess up how stem cells renew and are linked to cancer starting by piling up changes in Energy Unit DNA [95–98].
How Oxidative Stress Hurts Mitochondrial DNA
Oxidative stress hurts mitochondrial DNA (mtDNA), making it weak and adding to aging and disease.
Ways mtDNA Gets Hurt
Direct hurt comes when reactive oxygen types (ROS) hit mtDNA's building blocks and backbone, changing its shape and hurting its genetic truth. For example, tests with 200 μM of hydrogen peroxide showed that mtDNA gets three times more blocks than normal DNA[6]. Also, having less mtDNA makes it more likely to get hurt[7].
Indirect hurt comes when ROS go after other cell parts, which then hurt mtDNA. A key way is through lipid peroxidation. ROS hit mitochondrial membrane fats, making harmful things like lipid enals that stick to DNA. A study by Monroe et al. showed that such products - like 4-HNE, 4-HHE, and 4-ONE - start aging in human cells and mouse fat stem cells[8]. Notably, older mice (24–26 months) had nearly double the 4-HNE in their fat than younger mice (4–6 months)[8]. These bad things build up over time, hurting more even after the first ROS hit.
Together, these direct and indirect ways show why we need strong protein shields for mtDNA.
Proteins That Guard mtDNA
Many proteins help keep mtDNA whole. Mitochondrial transcription factor A (TFAM) covers mtDNA, giving some shield - not as much as histones do for normal DNA. DNA polymerase gamma (POLG) takes care of mtDNA copying and fixing, while the helicase Twinkle opens up the DNA to let this happen. These proteins work where nearly 90% of cell ROS are made during energy creation[5].
Even with these shields, oxidative stress still clearly harms mtDNA.
Examples of Oxidative Harm to mtDNA
Oxidative stress leads to many types of mtDNA harm. A common one is the making of 8-oxoguanine (8-oxo-dG), a changed base that can pair wrong during copying, causing lasting changes. ROS can also cause single-strand breaks by hitting the backbone, while double-strand breaks - where both strands are hit - are very bad and hard to fix. Empty spots, made when ROS remove DNA bases, weaken the genetic code even more. Studies show mtDNA hurt is 10 to 20 times worse than in normal DNA[9].
This buildup of harm makes a bad loop: sick mitochondria make more ROS, hurting mitochondrial work more and speeding up aging. Supporting this, a mouse study of heart damage showed a 44% drop in mtDNA in hurt hearts compared to normal mice[1].
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Fixing and Getting Rid of Bad Mitochondrial DNA
When bad stuff harms mitochondrial DNA (mtDNA), cells use two key ways to keep working: mend the breaks or throw out the bad mitochondria for good.
How Cells Fix Mitochondrial DNA
Fixing DNA base damage (BER) is how cells most often heal harm from bad oxygen in mtDNA. This way fixes usual breaks made by mean oxygen bits, like changed or added bases.
The BER way has five main steps. First, certain helpers called DNA glycosylases find and get rid of the bad base. These helpers can be simple (just taking off the base) or do two jobs (taking off the base and cutting the DNA chain). After the bad base is gone, a helper - AP endonuclease or a special kinase (for the do-two-jobs kind) - gets the DNA ends ready to fix.
Next, polymerase γ (POLG), the only DNA builder in mitochondria, fills the gap by adding right building blocks. At last, DNA ligase III closes the gap to end the fixing. If the harm is small or big, BER can fix a single block or several blocks. Cool fact: many of the mitochondrial fixer tools are tweaked versions from the cell core, changed by cutting bits or new message controls.
When the harm is too much to fix, the cell picks to remove it.
Taking Out Broken Mitochondria
If mtDNA breaks are too bad or the mitochondria can't work, cells start mitophagy - a way to throw out bad mitochondria. This stops too much bad oxygen bits and keeps the cell from dying.
"Mitophagy is a cellular process that selectively removes the aged and damaged mitochondria via the specific sequestration and engulfment of mitochondria for subsequent lysosomal degradation. It plays a pivotal role in reinstating cellular homeostasis in normal physiology and conditions of stress." – Kaili Ma et al. [10]
When mitophagy occurs, bad mitochondria get a mark for removal. They get wrapped by autophagosomes, which are special bag-like membranes. Then, these autophagosomes join with lysosomes, and there, the mitochondria are taken apart. Study has made it clear that stressed mitochondria can be picked out and taken out in many cell types, like brain cells and HeLa cells. Proteins like ATAD3B are seen as key in taking out damaged mtDNA by ways that do not need the common PINK1/Parkin method.
mtDNA Fix or Remove: A Look
Cells pick to fix mtDNA or take out bad mitochondria based on how bad the damage is. The table below shows the main ways these two choices differ:
| Aspect | mtDNA Fix (BER) | Mitochondria Take-Out (Mitophagy) |
|---|---|---|
| Main Aim | Mend harm in mtDNA | Get rid of the whole hurt part |
| Energy Use | Less – keeps mitochondria | More – needs new mitochondria |
| Speed | Fast for lone harm | Slow – takes many steps |
| Harm Level | Works for small harm | Starts with a lot of harm |
| Choice | Hits exact hurt spots | Takes the whole mitochondrion |
| Future Effect | Keeps the count of mitochondria | Must make new mitochondria |
When stress from oxidation causes small amounts of harm, BER can fix mtDNA well. But if the hurt goes past a key point - like when more than half of mtDNA bits change in some cell issues - a process called mitophagy kicks in to get rid of the bad mitochondria.
This two-way method makes sure that cells keep a good group of mitochondria. It balances fixing and taking out the bad parts to help keep the whole cell healthy and working right.
Keeping Mitochondrial DNA Safe from Harm
It's key to keep mitochondrial DNA (mtDNA) safe to make sure mitochondria work well and help you age in good health.
Ways to Live and Eat to Protect mtDNA
What you do each day can change how much stress your mitochondria face. Changing some habits can cut down on harmful oxygen types and make your body's defenses stronger.
- Light exercise: Doing regular, easy exercise helps your body fight off harm, making your mitochondria stronger [11].
- Eating well with antioxidants: Lots of fruits, veggies, whole grains, nuts, and seeds give you antioxidants that stop harm and protect mtDNA [12].
- Eating less often: This habit helps make new mitochondria and lowers stress on them [12].
- Staying away from bad air: Staying clear of cigarette smoke, dirty air, and strong chemicals cuts down on cell stress [11].
- Handling stress well: Good ways to deal with stress can lower overall stress and help mitochondrial health [12].
"Stabilizing mitochondria structure and energy efficiency is an obvious target for decreasing oxidative free radicals" [11].
Even though making life changes is key, taking some extra things can also help keep mtDNA healthy.
Stuff to Help Mitochondrial DNA Health
Along with changing how you live, some add-ons help guard mtDNA by cutting down stress from oxidation and boosting how mitochondria work.
- NMN (Nicotinamide Mononucleotide): This boosts NAD+ levels, which are vital for mitochondrial jobs. As NAD+ usually falls as we get older, NMN keeps cell work that saves mitochondrial health [13].
- Resveratrol: Known for fighting oxidation, resveratrol also turns on sirtuins, proteins that shield mitochondria from damage and help make life longer.
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Spermidine: This helps with autophagy, a cleanup process that gets rid of worn out mitochondria, cutting stress at the cell level.
"Spermidine clears out old and weak parts, like mitochondria, which slow cells down with their poor work and stress... These good things about spermidine are key and old" [13].
As we age, spermidine levels drop, so adding it helps [14]. - Fisetin: As a senolytic, fisetin gets rid of aged cells that can't split and cuts swelling, making a better space for mitochondria.
When mixed with a balanced life, these adds give a full way to guard mtDNA, not just through added things.
MASI's Way to Mitochondrial Health
MASI Longevity Science uses these steps by making adds just for keeping mitochondria healthy. Their items are well checked, made in Germany with top stuff, and checked in Switzerland. MASI's mixes - like NMN, Resveratrol, Fisetin, and Spermidine - are safe for vegans, free from allergens, and aim at key aging steps.
With nods from places like Harvard and the Mayo Clinic, MASI makes sure its adds line up with solid science. With over 352,000 members around the world, MASI mixes life actions and added things to look after mitochondrial DNA. Plans with price cuts up to 15% make it easy to keep getting support for mitochondrial care, working with the cell repair ways talked about above.
Wrap-Up
As we have seen, the repair and clear-out of cells are key in fixing mtDNA harm. Knowing how mtDNA takes hits is a big step in helping us age well and keep away disease. Studies show mtDNA gets hurt 10 to 20 times more than the core DNA, speeding up how fast we age.
The brain uses a lot of oxygen and has less guard against harm, so it is more at risk. Work shows that in people with Alzheimer's, mtDNA harm in the brain is 10 times more than in the core DNA. This shows we need to guard our cells, most of all in the brain. Given these facts, we need plans that are right on point.
But, we can take firm steps to fight this harm. Moving often, eating food full of good stuff, and handling stress well can cut down harm a lot. With added help like cell-boosting extras, we lay a strong base for cell health.
Main Points
Cell issues are often a big part of aging. Things like your diet and how you deal with stress touch your cell health. The best way to guard is by being forward-thinking and doing it all: take on good habits, eat well, and add well-proven extras.
For instance, MASI Longevity Science offers extras that meet these aims. Their goods aim for key cell paths - like upping energy with NMN and cleaning cells with Spermidine. With over 352,000 members all over the world, their answers are trusted to keep cells healthy.
Caring for your cells is not just about stopping disease - it’s about keeping up the energy and life you need to live well. By making smart choices and acting steady, you can impact the paths that lead to cell harm and keep up your cell health for a long time.
FAQs
How does harm to DNA in our mitochondria add to old-age sicknesses like Alzheimer's and Parkinson's?
Harm to the DNA in our mitochondria is key in old-age issues like Alzheimer's and Parkinson's, mostly because it stops the mitochondria from making power well. This mess leads to more oxidizing stress, most of all in brain cells, which need a lot of power always to work right.
When this DNA gets hurt, it starts protein folding wrong, brain cell death, and swelling - all of which are key parts in diseases that break down the brain. Over time, bad changes or parts lost in this DNA build up, making mitochondria work even worse and making these diseases move faster. Keeping mitochondria well is key to keep brain work good and help keep well for long.
