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Rejuvenation Research, Volume 10, Number 1

The latest Rejuvenation Research is available online, and microglia are the order of the day, it seems. Microglia are a component of the immune system, scavenging debris and defending the central nervous system. What is their role in the degenerations of aging, and what is there to be done about it?

Evidence That Aging And Amyloid Promote Microglial Cell Senescence

Advanced age and presence of intracerebral amyloid deposits are known to be major risk factors for development of neurodegeneration in Alzheimer's disease (AD), and both have been associated with microglial activation. However, the specific role of activated microglia in AD pathogenesis remains unresolved. Here we report that microglial cells exhibit significant telomere shortening and reduction of telomerase activity with normal aging in rats, and that in humans there is a tendency toward telomere shortening with presence of dementia. Human brains containing high amyloid loads demonstrate a significantly higher degree of microglial dystrophy than nondemented, amyloid-free control subjects. Collectively, these findings show that microglial cell senescence associated with telomere shortening and normal aging is exacerbated by the presence of amyloid. They suggest that degeneration of microglia is a factor in the pathogenesis of AD.

Cellular Therapy Using Microglial Cells

Recent insights into the function and dysfunction of microglia may inform future therapies to combat neurodegeneration. We hypothesise how different aspects of microglial activity including migration, activation, oxidative response, phagocytosis, proteolysis, and replenishment could be targeted by novel therapeutic approaches. A combined approach is suggested, encompassing opsonization and anti-inflamatory strategies in conjunction with an engineering of microglial precursors. Xenoproteases for bioremediation could be used to enhance intracellular and extracellular proteolytic capacity. The capacity of microglial precursors to cross the blood-brain barrier and to home in on sites of neural damage and inflammation might prove to be particularly useful for future therapeutic strategies.

One of the names attached to this second paper is John Schloendorn, who works on bioremediation research funded by donations to the Methuselah Foundation. "Xenoproteases for bioremediation could be used to enhance intracellular and extracellular proteolytic capacity" means "let's adopt some useful biochemicals from bacteria that can help microglia clean up cellular debris by degrading harmful metabolic byproducts." Our metabolism generates damaging chemicals as a side-effect of its operation. When these build up with age, they damage the workings of our cells - and thus damage the workings of our bodies. So why not try to help the body out by removing the source of damage?

Given that many types of bacteria consume human remains - and also consume the damaging biochemical junk that builds up in and between our cells - it stands to reason that researchers can find the basic components of biochemical tools in those bacteria that will enable us to safely decompose damaging chemicals while we're still alive. Given that some fraction of aging is due to the buildup of these compounds, that should benefit us greatly.

Shifting topics, here is another interesting paper; it doesn't sound like a practical line of research to me, but it's still an intriguing idea. A popular science article from yesterday is somewhat more informative for the layman than the abstract of the paper:

Food containing heavy isotopes of hydrogen, carbon and nitrogen could slow down the aging process. That's the claim of Oxford-based researcher Mikhail Shchepinov, who suggests that seeding key biological molecules with deuterium or carbon-13 could drastically reduce oxidative damage or even avert it altogether.

Reactive oxygen species (ROS) are a staple of ageing research, as they are believed to cause cumulative damage to biomolecules such as DNA, proteins, and lipids. Typically, breaking a carbon-hydrogen bond is the rate-limiting step of these reactions. But if the carbon or hydrogen atoms involved were replaced by a heavier version of the same element (13C or D), the reaction will be slowed down due to a well-established phenomenon known as the kinetic isotope effect.

...

Heavy water (D2O) is toxic to higher organisms, but Shchepinov argues that isotopes would only be incorporated in the sites that need to be protected from oxidation. 'Ideally, they will slow down the oxidation reaction so much that they will never be released to take part in other reactions. If some of them do break free, they will only occur in small concentrations,' he said.

As for the other folk quoted in the article, I'm dubious - it seems to me that the level of technology required to target the isotopes reliably (and keep them targeted) would enable far more effective methdologies of repairing rather than preventing oxidative damage.

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