aging

All posts tagged aging

Book review: Tripping over the Truth: the Return of the Metabolic Theory of Cancer Illuminates a New and Hopeful Path to a Cure, by Travis Christofferson.

This book is mostly a history of cancer research, focusing on competing grand theories, and the treatments suggested by the author’s preferred theory. That’s a simple theory where the prime cause of cancer is a switch to fermentation (known as the metabolic theory, or the Warburg hypothesis).

He describes in detail two promising treatments that were inspired by this theory: a drug based on 3-bromopyruvate (3BP), and a ketogenic diet.

Continue Reading

Book(?) review: Microbial Burden: A Major Cause Of Aging And Age-Related Disease, by Michael Lustgarten.

This minibook has highly variable quality.

Lustgarten demonstrates clear associations between microbes and aging. That’s hardly newsworthy.

He’s much less clear when he switches to talking about causality. He says microbes are the root cause of aging, and occasionally provides weak evidence to support that.

I still have plenty of reason to suspect that much of those associations are due to frailty and declining immune systems, which let microbes take over more. Lustgarten doesn’t make the kind of argument that would convince me that the microbe –> senility causal path is more important than the senility –> microbe causal path.

He has a decent amount of practical advice that is likely to be quite healthy even if he’s wrong about the root cause of aging, including: eat lots of leaves, green peppers, mushrooms, and use low pH soap.

One confusing recommendation is to limit our protein intake to moderate levels.

He provides a nice graph of mortality as a function of BUN (see here for more evidence about BUN), which hints that we should reduce BUN by reducing protein intake.

He also notes that methionine restriction has significant evidence behind it, and methionine restriction requires restricting protein, especially animal proteins.

Yet I see some suggestions that protein (methionine) restriction is likely only helpful in people with kidney disease.

My impression is that high BUN mostly indicates poor health when it’s caused by kidney problems, and doesn’t provide much reason for reducing protein consumption, and least in people with healthy kidneys.

Lustgarten has since blogged about evidence (see the 7/11/2018 update) that higher protein intake helps reduce his homocysteine.

I have also noticed a (noisy) negative correlation between my protein consumption and my homocysteine levels. But that might be due to riboflavin – when I reduce my protein intake, I also reduce my riboflavin intake, since crickets are an important source of riboflavin for me. So I want to do more research into dietary protein before deciding to reduce it.

The book is too quick to dive into technical references, with limited descriptions of why they’re relevant. In many cases, I decided they provided only marginal support to his important points.

Read his blog before deciding whether to read the minibook. The blog focuses more on quantified-self-style reporting, and less on promoting a grand theory.

I wrote this post to try to clarify my thoughts about donating to the Longevity Research Institute (LRI).

Much of that thought involves asking: is there a better approach to cures for aging? Will a better aging-related charity be created soon?

I started to turn this post into an overview of all approaches to curing aging, but I saw that would sidetrack me into doing too much research, so I’ve ended up skimping on some.

I’ve ordered the various approaches that I mention from most directly focused on the underlying causes of aging, to most focused on mitigating the symptoms.

I’ve been less careful than usual to distinguish my intuitions from solid research. I’m mainly trying here to summarize lots of information that I’ve accumulated over the years, and I’m not trying to do new research.
Continue Reading

I got interested in trying ashwagandha due to The End of Alzheimer’s. That book also caused me to wonder whether I should optimize my thyroid hormone levels. And one of the many features of ashwagandha is that it improves thyroid levels, at least in hypothyroid people – I found conflicting reports about what it does to hyperthyroid people.

I had plenty of evidence that my thyroid levels were lower than optimal, e.g. TSH levels measured at 2.58 in 2012, 4.69 in 2013, and 4.09 this fall [1]. And since starting alternate day calorie restriction, I saw increasing hypothyroid symptoms: on calorie restriction days my feet felt much colder around bedtime, my pulse probably slowed a bit, my body burned fewer calories, and I got vague impressions of having less energy. Presumably my body was lowering my thyroid levels to keep my weight from dropping.

I researched the standard treatments for hypothyroidism, but was discouraged by the extent of disagreement among doctors about the wisdom of treating hypothyroidism when it’s as mild as mine was. It seems like mainstream medical opinion says the risks slightly outweigh the rewards, and a sizable minority of doctors, relying on more subjective evidence, say the rewards are large, and don’t say much about the risks. Plus, the evidence for optimal thyroid levels protecting against Alzheimer’s seems to come mainly from correlations that are seen only in women.

Also, the standard treatments for hypothyroidism require a prescription (probably for somewhat good reasons), which may have deterred me by more than a rational amount.

So I decided to procrastinate any attempt to optimize my thyroid hormones, and since I planned to try ashwagandha and DHEA for other reasons, I hoped to get some evidence from the small increases to thyroid hormones that I expected from those two supplements.

I decided to try ashwagandha first, due mainly to the large number of problems it may improve – anxiety, inflammation, stress, telomeres, cholesterol, etc.
Continue Reading

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.
Continue Reading

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.

Continue Reading

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).