{"id":137,"date":"2013-09-02T12:47:47","date_gmt":"2013-09-02T12:47:47","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=137"},"modified":"2013-09-05T06:24:29","modified_gmt":"2013-09-05T06:24:29","slug":"new-take-on-free-radicals","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/09\/02\/new-take-on-free-radicals\/","title":{"rendered":"New Take on Free Radicals"},"content":{"rendered":"

One of the oldest and best-established theories of aging holds that we age because of oxidative damage. In the classic version, the body exploits high-energy chemistry based on oxidation for an energy supply at the cellular level, but this involves constant exposure to these high-energy species and the free radicals that are their by-products, species which can attack sensitive biomolecules. Damage to these molecules accumulates over a lifetime, so the story goes, and makes the body gradually less able to maintain its balance. I\u2019ve argued against the general idea that aging is an accumulation of damage, because of evidence that it is an active process, closely regulated like everything else about life. But new to me this week is a version of the theory by Spanish physiologist Gustavo Barja, in which some of the same chemistry is described as an active program of self-destruction. Barja argues that the process of burning fuel to produce energy can be extremely clean or it can be rather dirty. It is the \u201cleakage\u201d of free radicals during the process that causes the damage of aging, and this leakage can be quite fast, or it can be almost nil. Leakage is tightly-regulated in a way that determines life span. This is a unique lens through which to view aging. What does it help us to understand?<\/i><\/span><\/span><\/p>\n

An old and (I believe) discredited view of aging is that the body ages the same way a tool rusts or a car wears out over time – because damage accumulates with wear and exposure to corrosion. The best-established version of this theory is based on damage in the cellular energy factories, the <\/span>mitochondria<\/i><\/span><\/span>, and it is called the Mitochondrial Free Radical Theory of Aging, MFRTA. I visited last week with a man who has devoted his career to studying the chemistry of mitochondria, and he has come to believe that indeed mitochondrial chemistry has a lot to do with aging, but this is not just damage that accumulates as a side-effect of the energetic chemistry. He thinks that this damage is purposeful and programmed, and has written an updated version of MFRTA<\/a>.\u00a0<\/span><\/p>\n

Everything that you have heard about free radicals, ROS (reactive oxygen species) and anti-oxidants derives from the MFRTA. Mitochondria are tiny energy factories. Hundreds of them in each cell of our body burn sugar and convert the energy to an electrochemical form, analogous to charging a battery. This is the Krebs cycle<\/a>. The electrochemical energy (in the form ATP<\/a>) is then used for nerve signals and muscle movements and manufacturing biochemicals – everything for which the body requires energy.<\/span><\/p>\n

Classic MFRTA<\/span><\/strong><\/p>\n

In the original version of MFRTA theory, there are unavoidable by-products of the highly-energetic chemical reactions that power our bodies. These are free radicals or ROS, and they corrode the body\u2019s delicate chemistry. There are quencher chemicals – antioxidants that help mop up the toxic waste. These include SOD, ubiquinone (coQ10), and glutathione, catalase, and vitamin C. But they are not 100% efficient at preventing damage. It is the buildup of damaged biochemicals that is the root cause of aging.<\/p>\n

One of the attractive things about the MFRTA is its connection to evolutionary history. Once upon a time, more than a billion years ago, mitochondria were infectious bacteria. They invaded the primitive cells at the time, lived as parasites, and killed the cell with their powerful oxidative toxins. Over a long period of time, the parasites evolved to be friendlier to the host, and the host evolved to exploit the energy products of the parasite. Every eukaryotic cell, including all multi-cellular life today, is descended from this ancient symbiosis. Modern mitochondria are performing in the service of the host cell, and have no will of their own. But they retain the capacity to kill the cell, and in fact can serve as executioners when they are signaled to do so. This is apoptosis<\/i><\/a>, or programmed cell death.<\/span><\/p>\n

Problems with the MFRTA theory<\/strong> include:<\/p>\n