Prof. Charles Mobbs offered his critique here. Aubrey De Greys' rebuttal of Mobbs is here. Mobbs response to De Greys' rebuttal is here.
I have extracted my highlights, without the references, linking some of ADGs rebuttal in blue and Mobbs response to the rebuttal in red.
'The SENS strategy to treat symptoms rather than causes of aging has obvious and numerous flaws, any one of which would doom the strategy to failure'1) SENS treats symptoms, not causes
On the contrary, the symptoms of aging (age-related diseases and debility) are not targets of SENS:
rather, SENS targets their accumulating and initially inert precursors (“damage”), including indigestible
molecules, mutations and changes of cell number. Those are in turn caused by metabolism itself, but
that does not mean metabolism should be our sole target: just like a car, the human body needs
maintenance (repair of ongoing damage) as well as a robust design (to resist such damage), and
improving the design after manufacture is far harder than maintenance.
Aubrey de Grey concedes the fatal flaw of SENS: that it treats symptoms rather than causes of senescence, when he states that SENS would target “damage” that is “in turn caused by metabolism itself”. He states that SENS focuses on (symptomatic) damage rather than (causal) metabolism even though no strategy proposed by SENS has been shown to increase lifespan, whereas inhibition of metabolism is in fact a robust approach to increasing lifespan, based on genome-wide screening. Indeed, a simple antagonist of glucose metabolism mimics many of the protective effects of caloric restriction. This refutes his claim that “SENS is still probably closer to fruition than any alternative”. He attempts to mitigate this fatal flaw by comparing SENS with automobile maintenance, which analogy speaks for itself.
'Reversing specific age-related impairments without reversing ubiquitous age-related changes in protein oxidation and gene expression will not reverse senescence. The practical rationale for the SENS approach is that correction of the seven forms of damage can be accomplished “by techniques that… can (with adequate funding) probably be implemented in mice within a decade or so.” However, the major categories of damage each entail a multitude of specific impairments. Furthermore, it is not known which of these age-related changes actually predispose to functional impairments and which may be benign. Therefore SENS would require an impractically large number of interventions.'5) SENS involves impractically many individual therapies
Impractically many today, but my timeframe for SENS is long: I give it only a 50% chance of
succeeding in 25 years (ten in mice) even assuming ample funding. Also, this underscores why SENS
focuses on initially inert “damage” rather than metabolism: when the targets of therapies are
metabolically inactive, risks of unforeseen interactions between those therapies are minimised. Finally,
the SENS targets are far fewer than either their causes (the components of metabolism) or their
consequences (the aspects of age-related debilitation). Thus, even if my timeframe for SENS is
overoptimistic, SENS is still probably closer to fruition than any alternative.
'Finally, even if it were possible in some way to target the vast number of changes that occur during aging, at the moment, and indeed for the foreseeable future, the available technologies do not allow even one such modification to be carried out, much less the vast number necessary.'
7) No SENS therapy can be implemented with available technology
Incorrect on at least two counts: immune-mediated removal of neural amyloid (extracellular junk) and
pharmacological un-stiffening of the artery wall (extracellular crosslinks) were demonstrated in rodents
several years ago and are in clinical trials.
'The fundamental flaws of the SENS approach may be illustrated by an example. SENS is so simple as to be equally applicable to any disease: say, “Strategies to Engineer Negligible Diabetes”. Like aging, untreated Type I diabetes is associated with a vast number of impairments, including many in categories enumerated by SENS: cell loss and atrophy, mitochondrial abnormalities, course AGE-mediated extracellular crosslinking, and, of course, death. To treat Type I diabetes by a SENS-like approach of treating symptoms (e.g., using stem cells and growth factors to increase muscle volume and repair diabetic neuropathy) would be fatal. Instead, Type I diabetes is successfully treated by targeting the cause of the disease: replacing the missing insulin. Even better would be to replace the destroyed pancreatic beta cells with similar cells resistant to autoimmune destruction. Insulin therapy was developed, and beta cell replacement will be developed, not through the engineering-like approach advocated by SENS, but through basic research disdained by SENS.'Similarly, in type I diabetes, Mobbs says that beta cell replacement would be best and “will be developed” – but, contrary to his assertion, that is precisely the SENS approach to cell loss or any downstream consequences thereof.
'Even more damning, though, is that it has not yet been possible to develop a practical way to replace even this single cell type. The technical challenges entailed by SENS, including whole-body delivery of genes for somatic gene therapy, dwarf those posed by simple replacement of a single endocrine cell type. Multiply so-far unresolved problems posed by a single simple disease, by the vast number of age-related changes enumerated by SENS and the age-related changes not enumerated by SENS, and it is clear why SENS is not taken seriously.'