What is SENS?

The two main approaches to the problem of ageing are geriatrics and gerontology. Geriatrics is about trying to fix the consequences of metabolic damage that’s already been laid, rather than fixing the damage itself. The existing damage will stay right where it is and it will keep accumulating and causing more problems, making this approach an outstanding example of shoveling water with a pitchfork. Gerontology is about ‘patching’ metabolism so that it either stops causing damage or at least does so at a slower rate; it sounds awesome, but the catch is that metabolism is too complicated to hope to tweak it without causing annoying side-effects—like, uh, death.

metabolism No, it’s not the map of Hyrule from Legend of Zelda. It’s a map of human metabolism from Medicalxpress.com.

We have also mentioned the SENS approach, i.e. that of performing periodic, comprehensive maintenance of our bodies. We could let metabolism keep doing its business and lay all the damage it wants, and then periodically fix some of it, to prevent it from ever reaching a critical threshold. If this approach were to prove succesful, we’d be able to achieve in humans a property that only few species possess, the so-called negligible senescence. In a nutshell, organisms exhibiting negligible senescence don’t show any significant sign of biological ageing: Regardless of their age, their healthspan doesn’t change. They experience no functional decline, their reproductive abilities remain unchanged (whee!), and they aren’t any more likely to die as they grow older. Lucky bastards.

The question is, just how much damage we’d have to fix to get this approach to work?

The good news is, in the last thirty years of research, all the known types of damage fall under one of just seven categories. Different types of damage within the same category could be fixed using techniques only slightly different from each other. The bad news is, while after thirty years it’s unlikely we’ll find a type of damage that doesn’t fit any of these categories, these categories apply to what is currently considered a normal lifespan. In other words, there may be a type of damage that only occurs in humans 150 years old and older; we don’t really know, because no one has ever lived that long yet. So, even if we fix every damage type in all seven categories, there might still be unexpected problems ahead to fix. However, let’s not cross our bridges before we get there, and let’s have a look at the seven categories (or the ‘seven deadly things’) presently known.

(NOTE: This is just a lightweight introduction. If you want to get a deeper understanding, you’d better read Ending Aging by Aubrey de Grey. More information on him and on the SENS Research Foundation can be found on their website.)

The Seven Deadly Things

  1. Mitochondrial mutations: Mitochondria are ‘power plants’ producing energy in our cells. Their own genetic material is subject to mutations affecting the cell’s ability to function properly and eventually this leads to progressive cellular degeneration.
  2. Intracellular junk: The lysosome is the ‘incinerator’ of our cells—it breaks down stuff that is useless or harmful to the cell. Stuff the lysosome can’t break down accumulates inside the cells, eventually causing a wide range of old-age pathologies.
  3. Extracellular junk: Malformed, useless proteins accumulate between cells, impairing cell and tissue function. The infamous “plaques” of Alzheimer’s disease are an example.
  4. Cell loss and atrophy: Almost all our cells regenerate all the time, but with age, the regeneration process slows down. Eventually, cells regenerate slower than they die, leading to a lack of cells causing, among the others, the well-known fraility of old age.
  5. Cell senescence: Senescent cells are cells no longer able to divide. Instead of dying as they’re supposed to, they stick around and interfere with other processes—for example in other cells’s division, causing the decline of the immune system among other problems.
  6. Extracellular cross-links: Linking proteins keep cells together, but too many cross-links cause loss of elasticity, presbyopia, arteriosclerosis, and other problems.
  7. Cancer-causing nuclear (epi)mutations: Mutations in nuclear DNA can lead to cancer, a killing machine whose strength is the furious-paced reproduction of its cells.

The SENS (Strategies for Engineered Negligible Senescence) Platform

  1. MitoSENS: Overcoming the problem of mithocondrial mutations by means of allotopic expression of 13 proteins—copying the original mitochondrial DNA into the better-protected nucleus.

  2. LysoSENS: Making the lysosomes able to digest more types of junk by means of introducing into them genes that allows them to produce the necessary breakdown enzimes.

  3. AmyloSENS: Getting rid of the extracellular junk by enhanced phagocitosis (i.e. turning the immune system against the junk stuff).

  4. RepleniSENS: Using stem cell therapy to compensate for the missing cells.

  5. ApoptoSENS: Using suicide genes and immune stimulation to induce apoptosis (programmed cell-death) into senescent cells.

  6. GlycoSENS: Employing AGE-breaking molecules/enzymes (AGE stands for Advanced Glycation End-Products).

  7. OncoSENS At the end of the chromosomes inside the cellular nucleus are telomeres, ‘caps’ that prevent the chromosome from deteriorating. Normally, after each replication cycle, the telomeres of a cell shorten, and eventually when they’re too short the cell loses its ability to replicate. This process is partly compensated for by the action of telomerase, an enzyme that rebuilds telomeres. Cancerous cells, though, are such that this compensation gets out of hand, and thus they never lose their ability to replicate, causing the exponential growth of cancer cells. The answer to this problem could be WILT, the Whole-body Interdiction of Lengthening of Telomeres, that would work by halting telomerase production throughout the whole body, preventing cancers from growing forever. However, this would also cause normal cells to quickly lose their ability to reproduce, and thus there would be need to compensate for it, which could be done through interventions like RepleniSENS.

This description of SENS has been taken mainly from Wikipedia. Remember: This isn’t established science yet. The main goal of SRF is to get research done so that we can establish for a fact if this panel of interventions can really bring about the defeat of ageing, or if another plan needs to be devised. You can get in touch with Aubrey de Grey directly if you have questions or concerns about the SENS approach. As far as I know, he’s very responsive.

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