Strategies For Engineered Negligible Senescence - Framework


The ultimate objective of SENS is the eventual elimination of age-related diseases and infirmity by repeatedly reducing the state of senescence in the organism. The SENS project consists in implementing a series of periodic medical interventions designed to repair, prevent or render irrelevant all the types of molecular and cellular damage that cause age-related pathology and degeneration, in order to avoid debilitation and death from age-related causes.

De Grey defines aging as "the set of accumulated side effects from metabolism that eventually kills us", and, more specifically, as follows: "a collection of cumulative changes to the molecular and cellular structure of an adult organism, which result in essential metabolic processes, but which also, once they progress far enough, increasingly disrupt metabolism, resulting in pathology and death." He adds: "geriatrics is the attempt to stop damage from causing pathology; traditional gerontology is the attempt to stop metabolism from causing damage; and the SENS (engineering) approach is to eliminate the damage periodically, so keeping its abundance below the level that causes any pathology." The SENS approach to biomedical gerontology is thus distinctive because of its emphasis on tissue rejuvenation rather than attempting to slow the aging process.

By enumerating the various differences between young and old tissue identified by the science of biogerontology, a 'damage' report was drawn, which in turn formed the basis of the SENS strategy. The results fell into seven main categories of 'damage', seven alterations whose reversal would constitute negligible senescence:

  1. cell loss or atrophy (without replacement),
  2. oncogenic nuclear mutations and epimutations,
  3. cell senescence (Death-resistant cells),
  4. mitochondrial mutations,
  5. Intracellular junk or junk inside cells (lysosomal aggregates),
  6. extracellular junk or junk outside cells (extracellular aggregates),
  7. random extracellular cross-linking.

For each of these areas SENS offers at least one strategy, with a research and a clinical component. The clinical component is required because in some of the proposed therapies, feasibility has already been proven, but not completely applied and approved for human trials. These strategies do not presuppose that the underlying metabolic mechanisms of aging be fully understood, only that we take into account the form senescence takes as directly observable to science, and described in scientific literature..

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