Aging is a set of changes in your biochemistry, in the arrangement of atoms and molecules in and around your cells. Cells and the cellular environment are a connected web of delicate machinery - mess up their arrangement, and they stop working quite so well. One of the changes seen in our cells over time is an accumulation of chemicals that the body cannot break down. Eventually, this causes severe damage in cells due to a failure of recycling mechanisms, but issues arise well prior to that point.
Lipofuscin is the name given to a mix of many different types of chemical byproducts found in cells, long known to researchers. In particular, it is associated with a common cause of age-related blindness:
"Lipofuscin accumulation appears to be a major risk factor for macular degeneration, including the age-related type," said Dr. Rando. Toxic constituents of lipofuscin are generated as byproducts of the visual cycle, a complex chemical pathway that is required for the maintenance of the light gathering components of the eye called retinal photoreceptors.
The Methuselah Foundation funds a group working on the use of bacterial enzymes to safely degrade components of lipofuscin. One of those components is A2E, an early target for this research given the level of interest in this chemical in various branches of the scientific community. From last December's progress report:
In summer 2007, six undergraduate research assistants and one additional PhD candidate joined the effort at Biodesign Institute. They helped with synthesizing additional target compunds, such as A2E and CML (a major AGE). This veritable army of volunteers also was able to culture six independent degraders of CML, and identify two enzymes which break A2E in different ways.
Today, researchers at the Biodesign lab are working on identifying the enzyme initiating the breakdown of 7KC and CML. They are also characterizing the A2E-degrading enzymes further, and are preparing to move them into a cell model of age-related macular degeneration for initial safety and efficacy testing.
I noticed a paper today that explores biochemical mechanisms by which acculumated A2E leads to the damage of macular degeneration:
Although it remains unsubstantiated clinically, experimental results support that the accumulation of lipofuscin is related to an increased risk of choroidal neovascularization (CNV) due to age-related macular degeneration, a leading cause of legal blindness.
Here, we report that a major lipofuscin component, A2E, activates the retinoic acid receptor (RAR). In vitro [experiments] strongly suggest that A2E [induces] sustained activation of RAR target genes. A2E induced vascular endothelial growth factor (VEGF) expression in a human retinal pigment epithelial cell line [and] RAR antagonist blocked the upregulation of VEGF.
These results suggest that A2E accumulation results in the phenotypic alteration of retinal pigment epithelial cells, predisposing the environment to CNV development. This is mediated through the agonistic function of A2E, at least in part.
So A2E appears to drive the errant blood vessel formation of wet macular degeneration. Interesting.
As I often point out, all knowledge is useful, but we don't need to know exactly how lipofuscin accumulation contributes to age-related degeneration to know that it should be on the list of things to address as a part of any comprehensive repair of aging. Indeed, we don't even have to know exactly how it damages us in order to develop working methods of preventing that damage. More knowledge will make the task of eliminating lipofuscin-related damage easier - by narrowing the set of chemicals to target, by finding ways to render liopfuscin harmless without the effort of removing it, and so on. But by virtue of lipofuscin accumulation being a fundamental difference between young tissue and old tissue, we know that we should reverse it, and we have enough information at hand to start work on that problem immediately.