Fight Aging!

The SENS Research Foundation works on a new paradigm for medicine and aging: the goal is to repair the known underlying causes of degenerative aging so as to prevent and reverse its effects, creating actual rejuvenation in patients, and ultimately removing age-related disease and frailty from the world.

At present new biotechnologies needed for rejuvenation therapies are in the early stages of development. One line of this research involves removing accumulated metabolic waste products from the lysosome. Lysosomes are the recycling units of the cell, breaking down unwanted proteins and broken cellular machinery so that the parts can be reused. But they fail with age, largely because they become bloated with hardy waste products that they are incapable of breaking down. This leads to reduced cell maintenance, more damaged cells, and the consequent progressive failure of the biological systems and organs that those cells belong to.

All of this sizable contribution to degenerative aging could be prevented via the periodic application of suitable medical technologies, which is to say a means to break down and remove the compounds that the lysosome struggles with:

Cells are equipped with specialized "incinerators" called lysosomes, where they send damaged or unwanted material for destruction. Some cellular wastes, however, are so chemically snarled that even the lysosome is unable to shred them. With no way to eliminate these compounds, the cellular garbage simply builds up over time, progressively interfering with cell function. The disabling of specific cell types by their characteristic waste products drives numerous age-related pathologies. For instance, age-related macular degeneration (AMD) - the primary cause of blindness in persons over the age of 65 - is believed to be primarily caused by the progressive disabling of retinal pigment epithelial (RPE) cells in the eye, resulting from their accumulation of A2E, a kind of waste specific to RPE cells. Currently, there is no effective treatment for this form of AMD .

At the SENS Research Foundation Research Center (SRF-RC), our Lysosomal Aggregates team is working to efficiently deliver novel enzymes into the lysosome to degrade A2E . Extensive protocols have been developed which employ RPE cells derived from humans to be used as cell lines for the study of AMD. In our prior research, we identified many enzymes (e.g., manganese peroxidase) capable of degrading A2E in vitro, but were unable to efficiently deliver most of them to the lysosome. We are now working to develop ways to efficiently deliver the most promising identified enzymes into the lysosome of cells. One in particular (which we are calling SENS20) has demonstrated efficacy in degrading A2E not only in vitro but in A2E-loaded RPE cells.

In 2013, the SRF-RC team is in the process of putting SENS20 to the test, assessing its ability to degrade A2E in vitro and in RPE cells. We are also performing a variety of tests to assure ourselves that the enzyme and its activity are not toxic to the cell . The studies will build toward eventual testing of candidate enzymes in animals that develop A2E-driven blindness and - if successful - eventually towards human clinical trials. We are advancing toward preventing or curing macular degeneration with the first- of-class regenerative therapy for this debilitating disease.

Link: http://sens.org/research/research-blog/research-report-lysosomal-aggregates