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March 08, 2011

Deficiencies in the SENS Approach to Rejuvenation

Alcor - Deficiencies in the SENS Approach to Rejuvenation by Ben Best

Aubrey de Grey asserts that aging is the result of seven kinds of damage – and that technologies that repair all seven types of damage will result in rejuvenation. His seven-fold program for damage repair is called SENS: “Strategies for Engineered Negligible Senescence”. Dr. de Grey asserts that repairing aging damage is a more effective approach than attempting to slow or prevent aging, and I agree with him. Being an ardent supporter of SENS has not stopped me from simultaneously being a critic of aspects of his program that I think are flawed or deficient. I will attempt to outline some of my criticisms in simple language, assuming that my readers have some knowledge of basic science.

Two SENS strategies cannot justly be described as damage-repair, in my opinion. To protect mitochondrial DNA from free radical damage he wants to make copies of mitochondrial DNA in the nucleus – and import the resulting proteins back into the mitochondria. I would call this an attempt to slow or prevent aging – it cannot be called repair.



Similarly, SENS aims to eliminate cancer by deletion of genes that contribute to cancer, specifically telomerase and ALT (Alternate Lengthening of Telomeres) genes. I am not convinced that this is the best way to eliminate cancer, and I do not believe that deleting cancer-producing genes can properly be called damage-repair.

My criticisms about a procrustean attempt to force two strategies into a model purporting to only be concerned with damage and repair is minor, however, compared to a more fundamental concern that I have that a significant form of aging damage may be being ignored by SENS. I have written a review expressing my concern entitled “Nuclear DNA Damage as a Direct Cause of Aging” that was published in the June 2009 (22 pages) issue of the peer-reviewed journal Rejuvenation Research, [note 1] a journal of which Dr. de Grey is Editor-in-Chief. A PDF of my review is available in the life extension section of my website BENBEST.COM. Those interested in all the citations for claims I will make in this essay are encouraged to read my review. In this essay, I limit my citations to only a few critical articles.

There are many types of DNA damage, but for the purposes of this essay I will focus on breakage of both DNA strands – resulting in a gap in a chromosome. There are two mechanisms for repairing double-strand DNA breaks: Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). HR usually results in perfect repair, but HR can only operate when cells are dividing. NHEJ is the more frequent form of double-strand break repair, but it is error-prone. NHEJ is the only DNA repair mechanism available for non-dividing cells. Even in cells that divide, 75% of double-strand breaks are repaired by NHEJ.

Elimination of senescent cells and stem-cell replenishment of cells depleted in tissues by this elimination – as well as depleted by apoptosis – are part of SENS. But these strategies are only applicable to cells that divide – not to non-dividing cells such as neurons. Cryonicists are acutely aware that organs – and even whole bodies – can be replaced, but brains (neurons, axons, dendrites, and synapses, particularly) must be preserved if we are not to lose memory and personal identity. The ability of future medicine to replace all organs and tissues other than the brain would render most of SENS unnecessary – except for the brain.

SENS assumes without proof that nuclear DNA damage and mutation is negligible as a cause of aging (apart from cancer, apoptosis, and cellular senescence). This may be right or it may be wrong. I believe that without definitive proof, nothing should be assumed, and active investigation to determine the facts should not be neglected.

I believe the situation is not hopeless if nuclear DNA damage proves to be a significant cause of brain aging. Future molecular technologies for detection and repair of nuclear DNA damage could be significantly better than natural DNA repair enzymes. And, to simplify the required effort, the DNA repair technologies could be restricted to genes that are actively transcribed in neurons, rather than needing to repair the whole genome.

Further Reading

“Nuclear DNA Damage as a Direct Cause of Aging” that was published in the June 2009 (22 pages)

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