All posts tagged aging

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.

Political Calculations has a post with an interesting table of life expectancy in OECD countries. In addition to the standard life expectancy numbers, there is an additional set that is standardized to eliminate differences in a category of deaths that is roughly described as accidents and homicide (those least likely to be connected to healthcare problems).
I haven’t found an online explanation of how they were standardized (it’s apparently explained in the book The Business of Health: The Role of Competition, Markets, and Regulation by Robert Ohsfeldt and John Schneider, which I haven’t checked), and I can’t evaluate the extent to which their desire to promote the U.S. medical system has biased their methods.
What surprised me most was that it implies that the differences in what we normally think of as health and healthcare explain a surprisingly small part of the difference between national life expectancies. The actual life expectancy shows a difference of 3.6 years between the highest (Japan) and lowest (Denmark), but the standardized life expectancy shows a difference of 1.2 years between the highest (U.S.) and the lowest (U.K.).
This implies that national difference in traffic accidents, homicides, and some similar (poorly identified) causes of death are a good deal more important than the following differences: healthcare systems, diet, serious vitamin D deficiencies (which I expect to vary by latitude), FDA rules, and litigation of medical outcomes.

On a loosely related note, the book A Farewell to Alms mentions a report that 16th century Japan had an unusual absence of disease (but no indication whether it’s possible to get any quantitative evidence of this). This made me think of the alleged high Cuban life expectancy. Could relatively isolated islands be healthier due to lower influx of disease? Not that this would make isolation nice, especially since it might mean increased vulnerability to disease when contact with the outside increases.

Book Review: The Last Well Person: How to Stay Well Despite the Health-care System by Nortin M. Hadler
There appears to be a large discrepancy between how effective most people think modern medical practices are and the evidence that experts have presented suggesting that it does very little to extend life. This book gives the impression of describing a pattern of ineffective or harmful practices that might be offsetting the benefits of the practices that are known to work. But there are enough flaws in his argument that I can’t decide how much of his conclusions I should accept.
He starts by saying he’s a Popperian, but often acts like he’s following some other, more dogmatic, philosophy. I’m particularly annoyed at his certain feelings of inevitability that we will die by about age 85:

I am aware of no data to support the premise that we can alter the date of death. … When high-functioning octogenarians decline, it is because their time is approaching.

He starts by making a plausible claim that many people get cardiovascular surgery when there’s no evidence that it will benefit them (and is likely to create some risks).
But starting in the next chapter it becomes easy to find flaws in his arguments. He raises some plausible doubts about the evidence for statins, but then tries to imply that if the imperfect evidence that’s available shows that less than 2% of people who are prescribed statins will benefit, then we should doubt that those people ought to take statins.
He presents evidence that prostate cancer treatments save fewer lives than is commonly thought. It appears that sometimes the treatment merely changes the cause of death to something else. Yet he concludes that the treatment is useless, when the data he presents indicate nontrivial benefits. He hints that the evidence doesn’t meet the usual standard of statistical significance, but feels comfortable concluding (without even saying how close it is to being statistically significant) that the lack of proof is strong evidence of ineffectiveness.
He has a somewhat interesting proposal that the final phase of drug testing be done by the FDA rather than by drug companies. If the FDA were run by angels, that would solve a number of problems with the existing regulatory incentives, but with an FDA run by humans it would replace them with new problems. For instance, the choice of which drugs to test is something that only a few special interest voters (i.e. mainly those working for large drug companies) would understand, so their interests would be likely to influence those choices to the benefit of those companies.

The conference on Human Enhancement Technologies and Human Rights this past weekend had many boring parts and a few interesting tidbits.
Many of the speakers were left-wing ideologues who seemed to be directing their speeches only to others from the same small set of left-wing academics. There were fewer libertarians at the conference than I expected, but still enough that it was strange how much of a disconnect there was between the ideology shown in the speeches and the ideology I knew from elsewhere that many people held but were being quiet about.
There was plenty of concern about whether increased control over one’s body would decrease diversity, but I heard little that enlightened me on that subject. There have clearly been many technologies that increased diversity, such as tattoos. There are some that have decreased diversity because there is a substantial consensus about what’s best (e.g. eyesight – it’s unclear why we should be concerned about a shortage of people who can’t see well enough to drive). Then there are a few traits such as degree of autism where there’s some uncertainty whether reduced diversity would be good. There are some pontificators (I didn’t hear anyone this focused at the conference) who think they know better than the masses what the right amount of diversity is, and that their opinions should be imposed on the masses. But the evidence for the pontificators’ expertise and the masses propensity to make mistakes is generally underwhelming, so I can’t find much reason to be as concerned about the effects of enhancement technology as I am about the desire to impose expert opinion on those who don’t want it.
Hank Greely pointed out that the letter of the law authorizes the FDA to regulate anything that could be considered a body enhancement, including clothing. So only the FDA’s interest in obeying the spirit of the law will deter them from regulating external enhancements.
One amusing report of unwanted side effects of an enhancement technology is the increase in sexually transmitted diseases in seniors following the introduction of Viagra.
Aubrey de Grey made an interesting argument that the most effective approach to convincing people to support a cure for aging is to persuade them that they are being logically inconsistent when they fail to do so. He has a point, but it’s weaker than he thinks. He gave several examples of problems that were allegedly solved by persuading society to be more logically consistent, but I generally doubt that’s what happened. One example was tolerance of homosexuality. I see few signs that logical arguments had much effect on that. I think the biggest change came from peer pressure, which became increasingly popular as gays became able to migrate to places where there were enough gays to safely start exerting peer pressure. Another factor was the shift away from the belief that the main purpose of sex should be reproduction. That initially happened due to changing circumstances (reduced reliance on children to support elderly parents). I’d say that has generally produced beliefs that are more inconsistent as people abandon the least convenient symptoms of the belief (e.g. contraception) but are much slower to abandon symptoms that are remote from their experience. I think similar theories could be made about some other examples he gave (slavery becoming more expensive to enforce when railroads made it easier for slaves to escape to a non-slave state).