N. P. Schooler, J. Sheng
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY
Lipofuscin accumulates in the lysosomes of aging post-mitotic cells and progenitor cells, interfering with autophagy. Thus it has been proposed that the removal of this indigestible aging pigment may be a highly effective rejuvenation therapy. While current gene therapy experiments involving xenoenzymes look promising, there are still several drawbacks to such an approach, and the extent of therapeutic benefit remains to be seen. However, even though the lysosome uses enzymes to degrade its contents, this is not the only method known to modern science. It has been known for over forty years that pulsed unfocused lasers can selectively destroy pigmented structures without harming the surrounding tissue. Today this technique is widely used in dermatology clinics to remove everything from tattoos to age spots.
Ophthalmology research has shown that pulsed lasers selectively destroy aged Retinal Pigment Epithelial (RPE) cells that are loaded with lipofuscin, allowing new lipofuscin-free cells to repopulate the RPE, effectively rejuvenating the tissue. Experiments and modeling have both shown that with ultrashort pulses of the proper intensity, destruction can be confined to pigmented organelles while leaving the rest of the cell intact. Furthermore, it has been shown that wavelengths in the 700nm to 1100nm range can destroy pigmented structures at least several centimeters beneath the skin while leaving the overlying tissue unharmed. It is therefore our hypothesis that unfocused pulsed lasers can be used as a rejuvenation therapy to safely and selectively destroy lipofuscin in every tissue of a living organism.
To test this hypothesis, we are beginning with the nematode worm C. elegans as a model, since it is optically transparent, accumulates lipofuscin rapidly and ages rapidly. Our goals are to find the maximum intensity of a single 8ns pulse from our Nd:YAG laser that can be used without harming the worms, analyzing the amount of lipofuscin degraded, and comparing the lifespan of treated worms with untreated controls. The effects of different sublethal exposure levels and repeated treatment regimens will also be examined. While we have high hopes for the amenability of C. elegans to such treatments, we realize that more robust organisms, such as mammals, will be obviously be better suited, and such future experiments will be even more crucial. Thus we believe the well-established techique of using unfocused pulsed lasers to selectively destroy lipofuscin in vivo will be a very effective tool to reverse its deleterious age-related effects and thus repeatedly postpone aging.