Longevity Research

DNA Damage and Targeting Mitochondria

posted on January 21, 2008

Death is NOT the natural order of things. Overcoming death is.

For conscious intelligent beings, indefinite life eventually becomes the natural order.

Every life form fights for survival. But until now, there was no hope for avoiding decay and death.  In my humble opinion, the purpose of life is simply to keep on living, growing and thriving. Only with human intervention can we overcome death and achieve this. We humans, as an intelligent conscious species, finally thought our way to the threshold of open-ended life spans. Without intervention, every life form is doomed to personal oblivion. Evolved beings will always figure out how to survive.

I think about this a lot including Sunday afternoon a week ago when I attended an intimate discussion/brainstorm session. Some of my very favorite people were there. There were also some equally impressive quality people who I met for the first time. During the conference, and during discussions later with mostly new friends, I couldn’t help thinking about how they deserve to live indefinitely… and that our efforts just might insure they do. This was partly selfish of me, because I want open-ended time to develop new relationships with these fascinating people.

A common objection to living an unusually long time crossed my mind as well. It usually goes something like “I wouldn’t want to outlive all my friends”. This deathist phrase, at least to me, is the most illogical and idiotic reason for a death wish. First, if when we have a choice, and your friends choose to die, why would you let them drag you along? Second, if I can find some potentially cherished new friends in one afternoon, how many new friends do you think you could make in several more lifetimes? Granted, this was a select group that I was with a week ago. But they are certainly not the only interesting people in the world.

By the way, I didn’t hear anything but enthusiasm about the prospects for extreme longevity from this positive group.
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DNA DAMAGE AND TARGETING MITOCHONDRIA

"Does the accumulation of DNA damage in the cellular nucleus contribute to significantly to aging? How, if so? It is a topic for debate, with a weight of papers behind many of the consensus interpretations, but most of the community would answer 'yes' with some variety of qualifications. It isn't hard to find academic arguments for the role of DNA damage in most of the better known age-related degenerations. It's a matter of time, resources for research and scientific debate as to which pan out."

It is accepted that cancer is a consequence of DNA damage, but the relationships of other aspects of degenerative aging to accumulated mutations in our nuclear DNA are much argued. Is declining stem cell capacity with age caused in part by DNA damage, for example? A good question - and one that has yet to be answered in any firm manner.

Let's move on to your other DNA, contained in mitochondria, the power plants of your cells. Originally symbiotic bacteria, and now a vital cellular component, mitochondria have retained the functional portions of the ancient DNA they brought to the party. The weight of evidence for a connection between damaged mitochondrial DNA and aging is much greater than for nuclear DNA, and researchers are far closer to being able to do something about it:

"Your mitochondria are a source of a whole lot of biochemical trouble as the years go by. Damaged mitochondria proliferate in some cells and, like damaged factories, pollute the cells with excess reactive oxygen species and free radicals produced as metabolic byproducts. Each damaged cell then tries to maintain itself by exporting more reactive oxygen species and free radicals from its cell membrane structures, spreading the damaging pollution far and wide in the body.  Repairing or replacing damaged mitochondria is one way to strike at the root of this process, and a number of groups are working on that. The SENS research program identifies a different and even more fundamental way forward: create a backup in the cell nucleus for specific mitochondrial processes that cause all these problems when damaged."

"Another approach that's out there in the field is to target antioxidant chemicals to the mitochondria, where they can be effective in soaking up some fraction of the excess free radicals before they wreck havoc.
Antioxidants in general don't seem to be terribly effective when simply thrown at our biochemistry. While making a difference, targeted antioxidants are clearly only a delaying tactic - as opposed to repair strategies that can be performed indefinitely. This is what medicine looks like at the base layer these days - a lot of organic chemistry, building molecules that tweak other molecular machinery in a particular way. Manipulating mitochondria to reduce their contribution to aging and age-related disease is a growth field; you'll be seeing a lot more of it in the years ahead."

A THOUGHT FOR THE DAY ON AGING

"Brain aging is gradual brain damage. Some people think aging is wonderful and natural. That's tantamount to saying that brain damage is wonderful and natural."

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