aging

All posts tagged aging

Book review: The End of Alzheimer’s, by Dale E. Bredesen.

Alzheimer’s can be at least postponed for years in most people, and maybe fully cured.

The main catches: It only works if started early enough (and Bredesen only has crude guesses about what’s early enough), the evidence is less rigorous than I’d like, and it’s not a medical treatment, it’s a quantified self approach on steroids ketones.

My guess is that the book is roughly 70% correct. If so, that’s an enormous advance.
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Book review: Other Minds: The Octopus, the Sea, and the Deep Origins of Consciousness, by Peter Godfrey-Smith.

This book describes some interesting mysteries, but provides little help at solving them.

It provides some pieces of a long-term perspective on the evolution of intelligence.

Cephalopods’ most recent common ancestor with vertebrates lived way back before the Cambrian explosion. Nervous systems back then were primitive enough that minds didn’t need to react to other minds, and predation was a rare accident, not something animals prepared carefully to cause and avoid.

So cephalopod intelligence evolved rather independently from most of the minds we observe. We could learn something about alien minds by understanding them.

Intelligence may even have evolved more than once in cephalopods – nobody seems to know whether octopuses evolved intelligence separately from squids/cuttlefish.

An octopus has a much less centralized mind than vertebrates do. Does an octopus have a concept of self? The book presents evidence that octopuses sometimes seem to think of their arms as parts of their self, yet hints that their concept of self is a good deal weaker than in humans, and maybe the octopus treats its arms as semi-autonomous entities.

2.

Does an octopus have color vision? Not via its photoreceptors the way many vertebrates do. Simple tests of octopuses’ ability to discriminate color also say no.

Yet octopuses clearly change color to camouflage themselves. They also change color in ways that suggest they’re communicating via a visual language. But to whom?

One speculative guess is that the color-producing parts act as color filters, with monochrome photoreceptors in the skin evaluating the color of the incoming light by how much the light is attenuated by the filters. So they “see” color with their skin, but not their eyes.

That would still leave plenty of mystery about what they’re communicating.

3.

The author’s understanding of aging implies that few organisms die of aging in the wild. He sees evidence in Octopuses that conflicts with this prediction, yet that doesn’t alert him to the growing evidence of problems with the standard theories of aging.

He says octopuses are subject to much predation. Why doesn’t this cause them to be scared of humans? He has surprising anecdotes of octopuses treating humans as friends, e.g. grabbing one and leading him on a ten-minute “tour”.

He mentions possible REM sleep in cuttlefish. That would almost certainly have evolved independently from vertebrate REM sleep, which must indicate something important.

I found the book moderately entertaining, but I was underwhelmed by the author’s expertise. The subtitle’s reference to “the Deep Origins of Consciousness” led me to expect more than I got.

Book review: Aging is a Group-Selected Adaptation: Theory, Evidence, and Medical Implications, by Joshua Mitteldorf.

This provocative book argues that our genes program us to age because aging provided important benefits.

I’ll refer here to antagonistic pleiotropy (AP) and programmed aging (PA) as the two serious contending hypotheses of aging. (Mutation accumulation used to be a leading hypothesis, but it seems discredited now, due to the number of age-related deaths seen in a typical species, and due to evidence that aging is promoted by some ancient genes).

Here’s a dumbed down version of the debate:
<theorist>: Hamilton proved that all conceivable organisms age due to AP and/or mutation accumulation.
<critic>: But the PA theories better predict how many die from aging, the effects of telomeres, calorie restriction, etc. Also, here’s some organisms with zero or negative aging …
<theorist>: A few anomalies aren’t enough to overturn a well-established theory. The well-known PA theories are obviously wrong because selfish genes would outbreed the PA genes.
<critic>: Here are some new versions which might explain how aging could enhance a species’ fitness …
<theorist>: I’ve read enough bad group-selection theories that I’m not going to waste my time with more of them.

That kind of reaction from theorists might make sense if AP was well established. But AP seems to have been well established only in the Darwinian sense of being firmly entrenched in scientists’ minds. It got entrenched mainly by being the least wrong of a flawed set of theories, combined with some poor communication between theorists and naturalists. Wikipedia has a surprisingly good[1] page on the evolution of aging that says:

Antagonistic pleiotropy is a prevailing theory today, but this is largely by default, and not because the theory has been well verified.

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Book review: The Vital Question: Energy, Evolution, and the Origins of Complex Life, by Nick Lane.

This book describes a partial theory of how life initially evolved, followed by a more detailed theory of how eukaryotes evolved.

Lane claims the hardest step in evolving complex life was the development of complex eukaryotic cells. Many traits such as eyes and wings evolved multiple times. Yet eukaryotes have many traits which evolved exactly once (including mitochondria, sex, and nuclear membranes).

Eukaryotes apparently originated in a single act of an archaeon engulfing a bacterium. The result wasn’t very stable, and needed to quickly evolve (i.e. probably within a few million years) a sophisticated nucleus, plus sexual reproduction.

Only organisms that go through these steps will be able to evolve a more complex genome than bacteria do. This suggests that complex life is rare outside of earth, although simple life may be common.

The book talks a lot about mitochondrial DNA, and make some related claims about aging.

Cells have a threshold for apoptosis which responds to the effects of poor mitochondrial DNA, killing weak embryos before they can take up much parental resources. Lane sees evolution making important tradeoffs, with species that have intense energy demands (such as most birds) setting their thresholds high, and more ordinary species (e.g. rats) setting the threshold lower. This tradeoff causes less age-related damage in birds, at the cost of lower fertility.

Lane claims that the DNA needs to be close to the mitochondria in order to make quick decisions. I found this confusing until I checked Wikipedia and figured out it probably refers to the CoRR hypothesis. I’m still confused, but at least now I can attribute the confusion to the topic being hard. Aubrey de Grey’s criticism of CoRR suggests there’s a consensus that CoRR has problems, and the main confusion revolves around the credibility of competing hypotheses.

Lane is quite pessimistic about attempts to cure aging. Only a small part of that disagreement with Aubrey can be explained by the modest differences in their scientific hypotheses. Much of the difference seems to come from Lane’s focus on doing science, versus Aubrey’s focus on engineering. Lane keeps pointing out (correctly) that cells are really complex and finely tuned. Yet Lane is well aware that evolution makes many changes that affect aging in spite of the complexity. I suspect he’s too focused on the inadequacy of typical bioengineering to imagine really good engineering.

Some less relevant tidbits include:

  • why vibrant plumage in male birds may be due to females being heterogametic
  • why male mammals age faster than females

Many of Lane’s ideas are controversial, and only weakly supported by the evidence. But given the difficulty of getting good evidence on these topics, that still represents progress.

The book is pretty dense, and requires some knowledge of biochemistry. It has many ideas and evidence that were developed since I last looked into this subject. I expect to forget many of those ideas fairly quickly. The book is worth reading if you have enough free time, but understanding these topics does not feel vital.

Book review: Food and Western Disease: Health and nutrition from an evolutionary perspective, by Staffan Lindeberg.

This book provides evidence that many causes of death in developed nations are due to a lifestyle that is different from hunter-gatherer lifestyles.

His studies of existing hunter-gatherer societies show moderately good evidence that cardiovascular disease is rare, that aging doesn’t cause significant dementia, and shows weaker evidence of less cancer.

He has some vaguely plausible reasons for focusing on diet as the main lifestyle difference. I’m disappointed that he doesn’t mention intermittent fasting as a factor worth investigating (is it obvious from his experience that some hunter-gatherer societies don’t do this?).

He uses this evidence to advocate a mostly paleo diet, although with less fat than is often associated with that label.

Much of the book is devoted to surveying the evidence about other proposed dietary improvements, mostly concluding they don’t do much (or in the case of calorie restriction, might work by causing a more paleo-like diet).

I don’t have a lot of confidence in his ability to interpret the evidence.

He gives the impression that Omega-3 consumption has little effect on health, citing papers such as this review, whose abstract includes:

showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03)

I’d call that evidence for a moderately important benefit of Omega-3, and I consider it strong evidence in comparison to typical dietary studies, although it’s weak compared to the evidence that other scientific fields aim for.

One response from nutrition experts says:

The null conclusion of the Cochrane report rests entirely upon inclusion of one trial, DART 2.

A quick glance at recent publications from another author he cites (Mozaffarian) got me this:

Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil.

Excessive skepticism is probably better than hype, but it will discourage many people from reading it. Plus the style is somewhere in between a reference book and a book that I’d read from start to end.

The Personalized Life Extension Conference 2012 presented lots of ideas, with occasionally some science to back them up.

A lot of the advice backed up by the best science won’t be followed. In spite of the title of Brian Delaney’s Calorie Restriction talk, he didn’t have a solution to the problem of feeling hungry. When Max Peto reminded us of the dangers of sitting, the percentage of people who remained seated only dropped from maybe 97 to 95. There were vendors pushing food that had higher than optimal sugar content, and I think at least one pusher had some success.

I’ve been cutting back drastically on my vitamin/supplement consumption, and Stephen Spindler’s talk (arguing that most apparently good results in other animals were due to supplements inducing calorie restriction) has me thinking about cutting back farther to just fish oil and vitamin D.

The telomere guys still haven’t come up with a good theory for why evolution didn’t do the apparently easy thing and make some telomerase available to non stem cells, so I’m still assuming there’s some tradeoff such as cancer.

The most interesting talk was by David Asprey, describing an “upgraded paleo” diet – high fat, with careful attention to the quality of the fat. He has more ideas than he has time to communicate them.

Unfortunately he seems too busy throwing out new opinions to document the evidence behind them (or maybe the evidence is hiding somewhere on his poorly organized website). But in most cases he has a plausible paleo-like theory, and I’m generally confident they’d be little worse than a placebo, so I’m trying some of them.

At the moment that involves consuming more of some paleo-like foods that I’d already been starting to add to my diet. Grass-fed (Kerrygold) butter is possibly the most important, and coconut products are also rather high on the list. The butter tastes better than my dim recollection of butter from malnourished grain-fed cows. Coconut milk works well as a substitute for milk in dishes such as chowder and cream of onion soup.

Josh Whiton had an intriguing idea about trying to get the benefits of calorie restriction via a very low protein diet once or twice a week (with a paleo-like diet the rest of the time).

Book review: Counterclockwise: Mindful Health and the Power of Possibility, by Ellen J. Langer.

This book presents ideas about how attitudes and beliefs can alter our health and physical abilities.

The book’s name comes from a 1979 study that the author performed that made nursing home residents act and look younger by putting them in an environment that reminded them of earlier days and by treating them as capable of doing more than most expected they could do.

One odd comment she makes is the there were no known measures of aging other than chronological age at the time of the 1979 study. She goes on to imply that little has changed since then – but it took me little effort to find info about a 1991 book Biomarkers which made a serious attempt at filling this void.

She disputes claims such as those popularized by Atul Gawande that teaching doctors to act more like machines (following checklists) will improve medical practice. She’s concerned that reducing the diversity of medical opinions will reduce our ability to benefit from getting a second opinion that could detect a mistake in the original diagnosis, and cites evidence that North Carolina residents have an unusually high tendency to seek second opinions, and also have signs of better health. But this only tells me that with little use of checklists, getting a second opinion is valuable. That doesn’t say much about whether adopting a culture of using checklists is better than adopting a culture of seeking second opinions. The North Carolina evidence doesn’t suggest a large enough health benefit to provide much competition with the evidence for checklists.

One surprising report is that cultures with positive views of aging seem to produce older people who have better memory than other cultures. It’s not clear what the causal mechanism is, but with the evidence coming from groups as different as mainland Chinese and deaf Americans, it seems likely that the beliefs cause the better memory rather than the better memory causing the beliefs.

Two interesting quotes from the book:

certainty is a cruel mindset

to tell us we’re “terminal” may be a self-fulfilling prophecy. There are no records of how often doctors have been correct or not after making this prediction.

Convergence08 had an amazing number of interesting people in attendance. No one person stood out as unusually impressive – it was more that the average was unusually high for a 300 person gathering. I’ll list many small ideas, which partly reflects the fact that I was trying to sample a wide enough variety of sessions that I didn’t manage to absorb any one presentation in depth.
Genescient is a new company whose founders include SF author Greg Benford. It has a strain of fruit flies bred for lifespans more than 4 times normal, and has used their DNA to identify substances that might improve human lifespan. It sounds like they will soon offer dietary supplements which have little risk and a hope of slowing down aging by some hard to predict (probably small) amount.

Advice from Eliezer Yudkowsky (responding to a concern that transhumanists have few children): don’t reproduce until you can code your child from scratch.

Several ideas from a session run by Anders Sandberg:

  • AntiGroupware is designed to remove many social pressures from group decision-making
  • Once it’s easy to make copies of people, political campaigns will be run by a large number of copies. [This assumes that democracy can attempt to survive – are copies going to be denied votes?]
  • Politicians should be selected from losers of the game Diplomacy [It might be hard to keep them from deliberately losing, but with big incentives winning plus a low probability of any one loser becoming a politician, it might work.]

Ideas from a session run by Milton Huang:

  • Keeping Skype video connections open for hours at a time changes remote interactions between two people in ways that make them seem very different from telephone conversations, and more like being physically together
  • We should try to implement a way to transmit hugs remotely
  • We might be able to make people (especially those with autistic tendencies) experience more empathy via an “empathy machine” that measures and reports on what others are feeling

Ending Aging

Book review: Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime by Aubrey de Grey and Michael Rae.
This book makes a strong argument that the most important medical need in developed countries is to cure the damage associated with aging, rather than to combat the diseases which become serious as a result of that damage. It outlines a set of solutions which, if they can be implemented, look like they would add at least a decade or two to healthy lifespans.
All of the solutions look like they have a reasonable chance of being implemented within 20 years. But the probability of all of them working within that time is a good deal lower than the probability of any one solution working, and there’s no obvious way to analyze whether we can get significant health benefits without implementing all of the solutions.
The authors seem somewhat overconfident about most aspects of their proposed solutions, but that doesn’t affect the substance if their arguments very much. Even a small chance of postponing death and disability is worth a good deal of effort.
The parts of the solutions that appear hardest are the ones that rely on techniques similar to what are already being attempted by mainstream scientists (genetic engineering to add and delete genes from most cells in the body, massive use of stem cells, and moving enzymes across the blood-brain barrier). My impressions about the effort that has been put into these techniques and the results that have been produced so far suggest that at least one of these is likely to take much longer than the book asks us to hope for. The book gives one clear example of important research not living up to the hype surrounding it when it gives arguments that most cancer research is directed toward modestly postponing cancer rather than providing a full solution to cancer. I see no obvious way for a layman to tell whether the authors are relying on similarly overhyped research.
So even though the book gives convincing arguments that the goals of medical research ought to be reframed to focus on aging as the primary threat to be solved, it’s far from conclusive about whether that should imply a large change in actual research. It may be that the hardest and most valuable tasks are the ones that are already being worked on. Or it may be that one of the critical tasks is sufficiently hard that the most important need is to invent tools that are substantially more sophisticated than what’s used in existing research (i.e. that we most need something more radical that what’s proposed in the book, such as nanomedicine).

Cuban Health

A recent report makes surprising claims about the causes of the apparently impressive Cuban life expectancy data.
It says that shortages of cars, food, and reduced cigarette use had effects that were on balance healthy (I don’t see anything specific about whether a cigarette shortage caused the decline in smoking).
I had thought that there was strong evidence for the claim that increased wealth reliably correlated with increased health. It looks like I ought to examine the evidence on that subject more carefully.