The core mechanisms they talk about make sense, in particular transposons as root cause, and the picture of stressors competing for sirtuin activity.
The review of aging in yeast was a highlight. That’s a great example where the mechanisms were pretty clearly nailed down, and Sinclair was one of the people who figured it out.
I’m much more skeptical of the particular treatments discussed, and especially the proposal that NAD boosters ameliorate age-related diseases by boosting sirtuin activity specifically. NAD is a fairly general-purpose molecule, there’s a ton of other things it could be doing, and I don’t recall a demonstration that sirtuin activity mediates their effects. (If there is a mediation experiment, then that part is much stronger.)
Sinclair in general seems to fit the “great experimentalist, mediocre theorist” mold; the blabber about information loss and aging being epigenetic was thoroughly confused. He has a bad case of obsession-with-his-favorite-gene-class (namely the sirtuins). In this case that gene class seems to be adjacent to an actual root cause (transposons), but Sinclair himself doesn’t seem to have the conceptual framework in place to organize that knowledge.
The entire second half of the book is semipolitical fluff.
I think I would claim that the semipolitical fluff is probably the most valuable part of the book. In terms of moving the needle on mainstream acceptance, having a Harvard professor say fairly directly that “ageing is bad and we should cure it” is something I’d expect to make a significant difference.
Yeah, to be clear, semipolitical fluff is often valuable, and I agree that that’s likely the case here. But I don’t expect LWers to find anything new or interesting in that part of the book, nor is anything interesting there about how aging works. It’s for a different audience and a different purpose.
Yup, read it a few months ago. Mini-review:
The core mechanisms they talk about make sense, in particular transposons as root cause, and the picture of stressors competing for sirtuin activity.
The review of aging in yeast was a highlight. That’s a great example where the mechanisms were pretty clearly nailed down, and Sinclair was one of the people who figured it out.
I’m much more skeptical of the particular treatments discussed, and especially the proposal that NAD boosters ameliorate age-related diseases by boosting sirtuin activity specifically. NAD is a fairly general-purpose molecule, there’s a ton of other things it could be doing, and I don’t recall a demonstration that sirtuin activity mediates their effects. (If there is a mediation experiment, then that part is much stronger.)
Sinclair in general seems to fit the “great experimentalist, mediocre theorist” mold; the blabber about information loss and aging being epigenetic was thoroughly confused. He has a bad case of obsession-with-his-favorite-gene-class (namely the sirtuins). In this case that gene class seems to be adjacent to an actual root cause (transposons), but Sinclair himself doesn’t seem to have the conceptual framework in place to organize that knowledge.
The entire second half of the book is semipolitical fluff.
I think I would claim that the semipolitical fluff is probably the most valuable part of the book. In terms of moving the needle on mainstream acceptance, having a Harvard professor say fairly directly that “ageing is bad and we should cure it” is something I’d expect to make a significant difference.
Yeah, to be clear, semipolitical fluff is often valuable, and I agree that that’s likely the case here. But I don’t expect LWers to find anything new or interesting in that part of the book, nor is anything interesting there about how aging works. It’s for a different audience and a different purpose.
Yup, agreed.
(Unless you’re interested in how that kind of influencing is done, in which case it might make a useful case study.)