Piling in on Lipofuscin

Lipofuscin is one of the many different types of extracellular aggregates that contribute to aspects of age-related degeneration. It's one of the targets for the LysoSENS work funded by the generous donors who have given to the Methuselah Foundation. LysoSENS is a bioremediation approach - we know that all this junk in and around our cells in ultimately digested by soil bacteria, so we should get out there and identify the enzymes involved. This is a big job, but more hands speed the work.

LysoSENS is not the only program looking into tackling the accumulation of toxic byproducts of our biochemistry. Most of the others are characterized by a focus on one particular disease and its associated intracellular or extracellular accumulations. Thus, back we come to lipofuscin, via a release at EurekAlert:

Harvard Medical School announced today that is has signed a multimillion-dollar license agreement with Merck & Co., Inc. to develop potential therapies for macular degeneration ... Under the terms of the agreement, Harvard will receive a $3 million up-front payment, significant milestone fees and downstream royalties on any marketed products that result from this agreement.


Dr. Rando's approach is to prevent toxic substances called lipofuscins from forming in the eye. "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.

When light hits the retina, which is packed with photoreceptor cells, a complex chemical process occurs that stimulates the optic nerve. ... The most common by-products of the vision cycle comprise the lipofuscins, which are very stable toxic substances, and not readily eliminated from the eye.


One of the worrisome issues with the lipofuscins is that they are insoluble and form aggregates akin to plaques, suggested Dr. Rando. In addition, he noted the lipofuscins and their readily formed oxidation products are highly retinotoxic for a variety of reasons, which includes their propensity to react with DNA and other macromolecules.


Dr. Rando, members of his research team, and collaborators at Columbia University, selected small molecule antagonists that they had previously synthesized and showed that they can also stop production of the retinotoxic lipofuscins.

The more the merrier, and good luck to their team. As I've no doubt noted in the past, most of the seven pillars of Strategies for Engineered Negligible Senescence (SENS) are already engaged by the mainstream scientific community in connection with various age-related conditions. Progress towards lengthening the healthy human life span is being made, just not in a directed and efficient manner.

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