When it comes to recycling, the cells of our bodies put even the most eco-friendly people to shame. Almost every molecule in the cell is broken down and rebuilt on a regular basis; typical proteins might last anywhere from a few minutes to a few hours, while even “long-term” stores of fat persist for no more than a year or two. Even DNA, which notionally stays with a cell for its entire life, is regularly turned over in short stretches – guided by the sequence of the paired strand – to reverse the damage continuously being caused by stray radicals and background radiation.
The majority of this recycling takes place in the lysosome, a membrane-bound organelle full of strong acid and equipped with a whole complement of enzymes able to break down just about every kind of chemical bond that our metabolism knows how to create, or expects to encounter in the diet (since food and even pathogens taken up by a cell get routed to the lysosome too, for thorough digestion and reuse).
Cellular metabolism, however, is a tremendously complex network of biochemical reactions taking place in a very cramped space. By random chance, a side-reaction sometimes takes place to produce a substance so peculiar that the cell’s normal garbage disposal machinery has no tools on hand with which to break it back down. Although such events are very rare, their products – or “junk” – do begin to accumulate to a significant degree over the decades of a human lifespan.
In replicating cells, a small quantity of junk is of little concern; the quantity in storage is halved every time the cell divides, and so has little chance to build up to a pathological level. However, in non-replicating cells, such as the retina, the muscle of the heart, or neurons in the brain, the waste products do start to pile up – and just like an overflowing trash can, may begin to cause problems.
Two of the best-studied examples of the pathology caused by the accumulation of junk are age-related macular degeneration (AMD), a major cause of blindness affecting several million patients in the US atherosclerosis and age-related macular degeneration (ARMD) . Atherosclerosis is the disease of the arteries in which the vessels are gradually infiltrated by a buildup of fatty deposits as we age, making us progressively less able to endure exercise or achieve erections, and that ultimately kills and cripples us with heart attacks and strokes. ARMD, though less well-known, is the number one cause of blindness in persons over the age of 65 in the United States. Although very different in their presentations, both of these diseases share a common kind of origin: a form of cellular “indigestion.”
In the arteries, atherosclerosis begins when cells called macrophages try to protect our blood vessels from toxic cholesterol derivatives called oxysterols by swallowing them up, and then “digesting” them into harmless byproducts, using a specialized cellular structure called the lysosome. This protective action is successful – for a while. But eventually, each individual macrophage reaches the limit of its ability to go on taking in and processing more and more oxysterol, and each of them ultimately finds itself suffering with fatal indigestion. Perversely, damaged macrophages themselves accumulate in the inner layers of the arterial wall. This buildup of sickened macrophages in the arteries then triggers a series of further pathological processes, progressively clogging our arteries, inflaming our circulation, and ultimately sending a deadly clot hurtling through our bloodstream to the heart or the brain.
It’s a similar story when it comes to our eyes. There, the sacrificial guardian cells are called retinal pigment epithelial (RPE) cells, and their charge is to protect the light-sensing rod and cone cells in the back of the eye from a damaged byproduct of vitamin A metabolism called A2E. As RPE carry out their duty to degrade damaged structures in the back of the eye, they take in and attempt to process the toxic A2E they contain within them. Unable to process it, the buildup in of A2E in RPE ultimately kills them, leaving the rods and cones unprotected. Their bodyguards slain, the light-sensing cells degenerate and die, and vision slowly fades: darkness spreads outward from the center of the field of vision, ending in blindness.Thus, these seemingly-unrelated diseases have at their pathological core the same problem: an inability of the lysosome to degrade a toxic byproduct of metabolism. And as a result, both problems can potentially be cured by the same core approach within the rejuvenation biotechnology heuristic: the use of novel enzymes that are able to degrade the offending material (oxysterols in the macrophages; A2E in the RPE). By clearing out the toxic waste product that is destroying these cells and leading to dysfunction and disease, macrophages and RPE cells can be returned to normal function, and pathology can be prevented or reversed.To find such enzymes, SENS Foundation has tapped into the almost infinite diversity of microbial life on this planet: hardy organisms that have been shaped by the forces of evolution to survive in wildly-different environments, getting their “food” from an amazing variety of organic waste substances. By screening such organisms in the Foundation’s Research Center, and in collaborations with researchers at Arizona State, Columbia, and Rice Universities, we have sought out, identified, and isolated enzymes that break A2E and a key atherosclerosis-promoting oxysterol into simpler substances that the cell can more readily detoxify or excrete.Our work is now focused on modifying these enzymes to work better in the unique cellular environment of the lysosomes in the affected cells, and developing ways to target them. And there is every reason to think that the same strategy to a range of other diseases of lysosomal failure, which include several major age-related neurodegenerative diseases. All ongoing research points into the same direction: cells, just like people, can always benefit from
more effective recycling.
Ben Zealley works as a Research Assistant at the SENSfoundation as Assistant Editor of Rejuvenation Research. He has a long-standing interest in the reversal of human age-related degeneration, and is a graduate of Trinity College, Cambridge, where he studied biochemistry and pathology. In addition to SENS, he is broadly interested in the general field of human enhancement technology, particularly human/computer interfaces, and in nanotechnology.
Zealley, B., & de Grey, A. (2011). Commentary on Some Recent Theses Relevant to Combating Aging: October 2011 Rejuvenation Research, 14 (5), 561-565 DOI: 10.1089/rej.2011.1277
Michael Rae is employed by the SENS foundation as Research Assistant and a popular science writer with a strong focus on health and aging. He is the author of five scientific articles and commentaries in peer-reviewed scientific journals. Much of his work has been devoted to elucidating the SENS platform for anti-aging biomedicine for a popular audience.