SENS, the Strategies for Engineered Negligible Senescence, is an ongoing research and advocacy program that aims to bring aging under medical control. One day aging will be in exactly the same bucket as tuberculosis: it exists, it is a threat if you somehow lose access to modern medicine, but most people are never troubled by it. After watching the research community for more than a decade, I firmly believe SENS is the best path towards this goal, offering a shot at real working rejuvenation within our lifetimes if funded sufficiently. Aging is a matter of cellular and molecular damage, and SENS is in essence a repair program, outlining the shortest likely paths towards therapies that can revert the full list of known fundamental forms of damage that distinguish old tissue from young tissue.
SENS has been running as a research program for some years, albeit with far less funding that we'd like to see. A lesser known aspect of modern medical research is that near all early stage, proof of concept, high-risk work is funded by philanthropy. The better known institutional and for-profit sources of funding are risk averse and don't become involved until researchers already have demonstrations and prototypes. It's a wonder anything is ever accomplished, frankly. Thus SENS is funded near entirely by philanthropic donations. It has been since the days when research started under the auspices of the Methuselah Foundation, and this is still the case as it continues at the SENS Research Foundation.
One of the longer running SENS research programs is focused on mitochondrial DNA damage in aging, and an innovative way of dealing with this problem that was first pioneered by researchers working on inherited mitochondrial diseases. These conditions are very different from aging: in a genetic disease such as Leber's hereditary optic neuropathy a large fraction of a patient's mitochondria are dysfunctional from birth due to one or more damaged genes, whereas in a normal individual damage to mitochondrial genes accumulates over time as a side-effect of the operation of ordinary metabolic processes. Nonetheless, in both cases the damage is essentially similar and the same types of treatment will work. Genes encode protein machinery, and it is the proteins that are important. If the missing proteins can be supplied somehow, then it no longer matters that the genes are damaged. Thus the SENS plan, and the plan of researchers aiming to cure inherited mitochondrial diseases, is to place a copy of the crucial mitochondrial genes into the cellular nucleus.
Here is the latest in a series of articles from philanthropist Jason Hope on the nuts and bolts of the SENS research programs. This discusses work on mitochondrial damage in aging and how to make it no longer matter:
Various structures inside the cell read DNA like a set of instructions on how to do their jobs. A body cell keeps most of its DNA safely tucked away in its nucleus. Mitochondria are different in that they have their own DNA, known as mtDNA, that they use as an instruction booklet to make the proteins that make up the machinery they use to harvest energy from our food and convert it to ATP. Mitochondria are also different from other cell structures because they keep this mtDNA nearby instead of storing the set of instructions in remote location inside the nucleus.
Just like municipal power plants, mitochondria create toxic waste as a byproduct. This toxic waste can pollute the surrounding cellular community and cause damage to structures within the cell. Mitochondria power plants spew out free radicals that impart particular damage to cellular structures. Because of proximity to the power plant, mtDNA is at special risk for exposure to toxic waste. Free radicals can assault vulnerable mtDNA and delete large chunks of genetic code. This can render the mitochondria incapable of reading the instructions for making the critical components these little power stations need to create energy.
To make matters worse, cells tend to hang on to mutant mitochondria while destroying healthy ones. As a result, once even one mitochondrion with these large deletions appears, its progeny quickly take over a healthy cell. In a perfect world, scientists would simply prevent deletions in mitochondrial DNA or repair deletions before they cause harm. Unfortunately, science is nowhere near ready to prevent or repair mtDNA deletions. For now, the most reasonable approach is to engineer a system that protects cells from damage caused by mutant mitochondria. One way of doing this is to create backup copies of mtDNA and safely tuck them away in the cell's nucleus, where free radicals cannot harm the information contained within the mitochondrial genes.
This approach of making backup copies is not new - evolution has already moved thousands of genes that were originally part of the mtDNA into the protective confines of the nucleus. Today, the mtDNA that mitochondria keep near the power plant contains instructions to build only the 13 different proteins it needs on a day-to-day basis, even though it originally contained over a thousand. The others are now safely ensconced in the nucleus. When accessed, these genes create proteins in the main body of the cell, outside the mitochondria. The cell then imports the newly created proteins into the mitochondria through specialized transport docks in the mitochondria membranes.
The greatest challenge to importing the 13 remaining proteins is that they tend to fold up on themselves while in the main body of the cell, creating folded structures too large to fit through the transport docks. Scientists at the SENS Research Foundation Research Center are working [on] ways to allow decoding the "working copies" of backup copies of genes whose proteins are destined for the mitochondria to occur near mitochondria rather than far away in the cell body. Because they do not have so far to travel, proteins may pass through transport docks before they fold up.
This new approach was pioneered by Professor Marisol Corral-Debrinski at the Institut de la Vision at Pierre and Marie Curie University, Paris. SENS Research Foundation funding helped Dr. Corral-Debrinski's team introduce into the eyes of a rat a mutated mitochondrial gene associated with an inherited form of blindness to cause vision loss in the lab animal. Using the same technique, the team then restored the rat's vision.