(Added: You can probably get the The Paleolithic Prescription here.)

The researchers noticed that there were differences in lifeways between these exemplary foragers and industrialized people’s of the West that seemed related to health and well being. They were able to link, sometimes definitively, sometimes tentatively, diet and activity levels on one hand and health on the other. Their findings, by the way, were first published in the peer reviewed literature, then turned, by the scientist themselves, into a popular book. (One of the findings eventually led to the understanding that there are different kids of cholesterol, which seem to have very different health related implications.)

My own research with the Efe (Pygmies) of the Ituri Forest, in Zaire, was an indirect offshoot of that early work. I got my PhD at the same institution, Harvard’s Anthropology Department that housed much of the Kalahari project, and the Ituri project was started by the same leader, Irv DeVore, via his students. So, the tradition of examining the lifeways of modern day foragers, in part to understand ideal human conditions, and comparing those conditions to western ways continued.

Meanwhile, one of the graduate students at Harvard, Peter Ellison (yes, he is related to that Ellison) had been interested in some work coming out of Harvard Medical school looking at hormones and behavior, especially as related to reproductive biology of human women. Building on that work, Ellison created an entirely new field of study, called “Reproductive Ecology.” He finished his PhD and was added to the faculty at the Anthropology department in one of those in between positions (as was I and many others over the years) but Peter became one of the very few such individuals to be eventually offered a tenured position with the most “always hire from outside” institutions ever. And Ellison created the Reproductive Ecology Lab within the biological anthropology wing of Harvard’s Department of Anthropology.

And, they studies the heck out of female reproductive ecology. I had the pleasure of working, almost every semester that I was there from late in my PhD cycle through my post-PhD teaching career there, to work with Mary O’Rourke (and others) who were from that lab running an undergraduate tutorial. The tutorial is three or four faculty members each running two or three groups, with about five or six students in each group. These are students majoring in Biological Anthropology, who have already taken a class or two but are on their way into the research labs. The tutorial instructors’ job is to turn these young and interested minds into the minds of proto-Anthropologists by carefully examining a different topic each week, looking at a combination of peer reviewed literature and secondary but excellent literature (back in those days, the former was easier to find).

So, I spent a lot of time hanging around with the Reproductive Ecology people (and, by the way, collecting some of their data in Zaire). Every social event had a lot of Repro Eco folks at it, so it was pretty normal for someone to pull out a box of specially prepared test tubes to get every one to provide saliva samples for some study or another. It was not long into the process of developing this subfield that the reproductive ecology of men, simpler but still important, was also taken up by this group, so everyone had an opportunity to spit into the tubes. For example:

Hypothesis: Testosterone in men varies over short time scales (of minutes, hours) during a poker game depending on which cards they are dealt, assuming the samples are not contaminated by …

… oh, never mind, you get the picture.

Anyway, it was while I was a couple of years into my own graduate career when a young man from California showed up to study anthropology, with a particular interest in Biological Anthropology. It was Richard Bribiescas. Rick and I did not hang around a lot of time, because we were both busy, but we were good friends and broke bread (a euphemism for guzzling beer but there were also tacos and cheeseburgers) quite often.

When Rick got to Harvard, there was already a strong tradition of working to understand modern human problems in the Western world by examining modern human behavior and physiology in a variety of other societies, including foragers.

Many young men and women went to the field from that department, to work in Poland, Borneo, the Amazon, the Congo. Among those, very few attempted to work in the most difficult of conditions, in a rain forest with foragers. Of those who tried most retreated and picked another topic. A few persisted and continued to study this or that thing about one of the few remaining forager group son the planet. That’s what I did, with the Efe. That’s also what Rick did, with the Ache, of South America.

And, as a result of that, Rick produced a bunch of interesting peer reviewed papers, and eventually, a book that has been out for a while now called Men: Evolutionary and Life History. A number of books had been written about female reproductive ecology, but along the way, rick became the expert on male reproductive ecology, discovering that it is not as simple as one might expect. This book is the result of that achievement.

And now, Rick is an old guy. He must be at least 45. And, as such, he has turned his attention to a new but related topic: How do men age. And, the newly produced book that comes from this research to your book shelf is How Men Age: What Evolution Reveals about Male Health and Mortality

Do not buy or borrow some book on aging written by a web site, a fake MD, or some other charlatan. Read a book on aging (in men) that first appeared many times in the peer reviewed literature, written by Harvard Trained Yale Expert Richard Bribiescas.

Note the subtitle. This is about what evolution reveals about male health and mortality. Having taught along side him many times, and after all those beers, tacos, and cheeseburgers, I can tell you that Rick knows all about evolution, and of course, he is the world’s leading expert on male reproductive ecology.

I put the Table of Contents below to give you and idea.

Rick is a great writer, and this book is fun to read.

Do the well known features of male aging have some sort of evolutonary advantage, as has been proposed for females? How much of male aging in the West is a function of our Western lifestyle, or a function of our seemingly extended lifespan? What about the contradiction between what we mere humans think of as “health” or “healthy” and what the cruel and cold process of Darwinian natural selection things about such silly things? What about sex, relationships, monogamy, polygamy, fatherhood and child rearing, in male humans in general, and across the aging process? And our brains, our obscenely large brains, what the heck are they for?

You will enjoy this book, especially if you are a man of a certain age.

Table of Contents:

Acknowledgments ix
Chapter 1 A Gray Evolutionary Lens 1
Chapter 2 Dead Man’s Curve 17
Chapter 3 Getting a Handle on Love Handles 45
Chapter 4 Older Fathers, Longer Lives 70
Chapter 5 Dear Old Dad 88
Chapter 6 Darwinian Health and Other Contradictions 106
Chapter 7 Older Men and the Future of Human Evolution 133
Notes 145
Index 169

In homage to an inspiration of this post, I provide this link to the secret, generally unseen obituary of Professor Irven Boyd DeVore.

Here’s the summary of the paper:

NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice, by
Hongbo Zhang, Dongryeol Ryu, Yibo Wu, Karim Gariani, Xu Wang, Peiling Luan, Davide D’Amico, Eduardo R. Ropelle, Matthias P. Lutolf, Ruedi Aebersold, Kristina Schoonjans, Keir J. Menzies, Johan Auwerx, (here, if you subscribe to Science.)

The oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) is critical for mitochondrial function, and its supplementation can lead to increased longevity. Zhang et al. found that feeding the NAD+ precursor nicotinamide riboside (NR) to aging mice protected them from muscle degeneration… NR treatment enhanced muscle function and also protected mice from the loss of muscle stem cells. The treatment was similarly protective of neural and melanocyte stem cells, which may have contributed to the extended life span of the NR-treated animals.

Writing in Science, Leonard Guarente notes:

NAD was discovered over a century ago, and its role in cells as a redox conduit in metabolism was subsequently established. More recently, its oxidized form, NAD+, resurfaced as a key molecule in aging in organisms ranging from yeast to mammals by the finding that the antiaging proteins, sirtuins, are NAD+-dependent deacylases. These proteins play a key role in mitochondrial function. Indeed, aging is also associated with loss of sirtuin and mitochondrial function.

As to whether NAD+ replenishment can improve health maintenance in humans, it has been reported that cellular NAD+ amounts decline during human aging (11). Also, the strict conservation in the relevant pathways of NAD+ synthesis, sirtuins, and PARPs suggests that NAD+ replenishment may also provide health benefits in people. Still, it will be important to test in humans whether dietary supplementation with NAD+ precursors will raise cellular NAD+ concentrations sufficiently to compensate for the loss due to aging. If so, it will also be necessary to test, in rigorously controlled trials, whether raising NAD+ concentrations improves health parameters, such as blood glucose and lipid profile, as well as inflammation. More expanded trials could measure effects on bone density, endothelial cell function, muscle mass, or even cognition. If NAD+ precursors can positively affect health parameters, it is reasonable to anticipate their place at the table alongside more traditional pharmaceutical drugs in the treatment of diseases.

And yes, you can buy this stuff.

But before you do that you may want to check out some of the writing that comes up from the Skeptical Search Engine.

The short answer to this is, I’m not really sure, but I think it is helpful to put aging, and changes in human patterns of aging, in a broader anthropological and evolutionary perspective.

When we look into the past, it is too easy to compress our ancestry into a caricature of primitive humanity, and based that conception on the wrong model. For example, it is said that “people were shorter back then.” Often, that is true, but the shorter people were actually poor urban dwellers in late medieval European settlements where diet was poor and disease demanded more energy of the immune system than average, so growth was sacrificed. If we look at pre-agricultural foraging populations, we often see relatively tall people. This is a bit enigmatic because so many modern forager groups are short statured. The explanation for that is probably that forager groups who are still around today, or have been extant over the last century or so, eek out their existence in relatively marginal habitats, the better parts of the landscape taken over by farmers and herders.

___
See: “If this was the Stone Age, I’d be dead by now”
___

So, we should expect that prehistoric lifespan varied across time and space, and as I noted, there were probably always elderly people, but just not too many of them, compared to today. It has become axiomatic to note in modern day conversations that many of our diseases, in the West, are “diseases of civilization.” This is a combination of health effects, but one of the most important is the lack of disease of the past because they have been addressed, at least for now, at least for a subset of the human population. Antibiotics alone probably allow a much larger proportion of the human population to survive long enough to experience age-related disease.

A good part of Howard’s documentary is about the science of aging. We want our scientists to figure out how to beat aging, or at least, slow it down. But this is not easy. Humans are primates, and primates are mammals. The very earliest mammals probably evolved to die young. That seems counterintuitive but it really isn’t. Life History Theory predicts that organisms will be selected to produce some sort of balance (or bias, imbalance) of three major energy shunting systems: growth, maintenance (including the immune system), and reproduction. Humans reproduce slowly, producing one (or two) offspring at a time, and putting a lot of effort into each one. This goes along with a long lifespan, because in order to produce a small number of high-quality offspring one must take some time. This, however, places additional demands on the immune system. In order to keep up with evolving microbes and the overall ravages of time, we need to spend a fair amount of effort on keeping from being too sick. And, we happen to be large, for a primate. That probably relates to predator pressure and a few other factors. So while we are selected to live a long time compared to the average primate (and certainly, the average mammal) we can only go just so far.

But perhaps more importantly, we (humans, and to a somewhat lesser extent, primates in general) are modified versions of mammals, and there are indications that mammals were never originally designed (by natural selection) to live long lives. Early mammals were probably small, and small goes along with a short lifespan in the mammalian world. Remember, those early mammals were living along side dinosaurs! (There were large early mammals but modern mammals, including all the more recent large one, probably evolved from a subset of them that were on the small side.) In a world where the smallest dinosaurs were larger than the largest mammals (or close to that) mammals were probably more often prey than predator. The best strategy if the most likely cause of death is being scarfed up by something larger is to live fast, have one or two litters of offspring, and do the whole “circle of life” thing really fast.

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See: How Long Is A Human Generation?
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One strong piece of evidence that a live fast and die young strategy applied to early mammals is the fact that mammal females are born already containing all the egg cells they will ever produce. This is the primary determinant of reproductive lifespan for human females. Organisms that are born ready to reproduce tend to have that strategy of rapid early reproduction followed by an early death. One of the more extreme examples of this is aphids. Aphids have two modes of reproduction, but in one of them, female aphids are born gravid. While human females are not born pregnant, they are born with the eggs ready to go.

Not only have humans (following the primate lead) extended their lifespan and slowed down their reproduction, but they ave added, apparently, another phase of life: Post reproductive. Human females in foraging societies around the world are productive members of their families after they have stopped being fertile. This seems to not make sense from a Darwinian perspective. Why not just keep reproducing until you die? Probably for two reasons. First, they can’t, because human lifespans are already extended to the limit of our phyolgeneticaly constrained abilities. Second, that post-reproductive period probably enhances Darwinian fitness. Studies have shown that elder women in foraging societies contribute significantly to the health and wellbeing of their own children’s offspring. Grandmothers are an adaptation!

But first, let’s look at the method used in this study, because that may be almost as important as a development. And for this, we will use a sports analogy.

Let’s say there’s an allele (an allele is a variant of a gene) that can boost your ability to play baseball. It really works. It causes an eye-hand coordination thing that improves batting, catching, and also affects your perception of movement in 3D space so you never miscalculate whether to throw or hold the ball or run vs. stay on base.

If you checked for this allele in professional baseball players, you might find that many have it, and even that there looks like there may be more copies of this allele in the overall genome of Major League Baseball, but perhaps at a statistically non-significant level. Yet, you are pretty sure this allele exists and has this effect.

Well, you really didn’t want to test the hypothesis that this allele causes a person to be a professional baseball player. Rather, the allele causes this special hand-eye thing, which is a trait … a phenotype … that then would make a person a great baseball player. But there may be other ways to be a great baseball player, and there may be lots of things a person with this allele may end up doing.

So, you could re-do your statistical analysis by looking not for whether someone is an accomplished baseball player, but rather whether or not they have this hand-eye coordination trait. Then, you figure out a test for the trait, and a test for the gene, develop a sampling strategy that ignores one’s involvement in baseball, and bingo, you’ve got a statistically significant result!

That is an increasing trend in genetic studies of traits (especially disease-related traits). The term that has emerged (but is not the only term used) is “endophenotype.” The endophenotype in the fictional but plausible example I gave above is a super excellent genetically determined hand-eye coordination. In the study just released as you were reading the above paragraphs, it is something physical that seems to be related to the progression of Alzheimer’s disease.

The endophenotype is a version of a protein found in cerebral spinal fluid, called CSF ptau₁₈₁. If a cell was a house, microtubules would be the 2X4s and other pieces of wood. The house would be made of them, and some of them would be used for other purposes as well. Microtubules make up the cytoskelton of a cell and are involved in a lot of day to day cellular processes. Microtubules are therefore very important, and they are made up of tiny protein globs called tubulin. So, the exact structure of tubulin, which is mostly determined by the genetic code that specifies it, has important cascading effects. The tau genes code for “tau proteins” which interact with tubulin as it is being assembled into microtubules, in particular, in the Central Nervous System. Small variations in Tau DNA can cause variations in Tau proteins that could then affect microtubule formation or stability. Thus, the potential connection between certain Tau alleles and, in this case, Alzheimer’s disease.

The current study looked at DNA variants in 846 patients and found a link between rapid progression of Alzheimer’s and the suspect pTau protein.

“We have looked at data from three separate, international studies, and in all three, we found the same association. So we are confident that it is real and that this gene variant is associated with progression in Alzheimer’s disease,” said first author Carlos Cruchaga, PhD.

In particular, the researchers report the link between this slightly variant DNA (called rs1868402) and higher levels of the CSF ptau181 protein, and a faster rate of progression of the disease. This does not seem to be linked to the risk of having Alzheimer’s or to the age of onset, which makes sense because increased levels of the protein levels is not associated with onset, nor does it occur prior to the clinical visibility of the disease.

Can this knowledge help? Probably. The researchers suggest that rs1868402 or some other variant ultimately causes a change in metabolic processes that lead to a pathological form of tau proteins, which would cause neurodegeneration. A similar metabolic glitch, if induced in mouse brains, affects neural function, supporting this idea. So there are two potential benefits: 1) Identifying those who are likely to have rapid degeneration among clinically new Alzheimer’s patients; and 2) Developing a pharmaceutical intervention to fix the degeneration process now that it is (probably) better understood.

Cruchaga, Carlos, Kauwe, John, Mayo, Kevin, Spiegel, Noah, Bertelsen, Sarah, & Et.Al. (2010). SNPs Associated with Cerebrospinal Fluid Phospho-Tau Levels Influence Rate of Decline in Alzheimer’s Disease
PLoS Genetics, 6 (9)

In neurodegenerative diseases specific proteins escape the cell’s quality-control system and associate together, forming insoluble aggregates. … we discovered that the aging process itself, in the absence of disease, leads to the insolubilization and increased aggregation propensity of several hundred proteins in the roundworm Caenorhabditis
elegans. These aggregation-prone proteins have distinct structural and functional proprieties. We asked if this inherent age-dependent protein aggregation impacts neurodegenerative diseases. We found that proteins similar to those aggregating in old worms have also been identified as minor components of human disease aggregates. In addition, we showed that higher levels of inherent protein aggregation aggravated toxicity in a C.
elegans Huntington’s disease model. Inherent protein aggregation is a new biomarker of aging. Understanding how to modulate it will lead to important insights into the mechanisms that underlie aging and protein aggregation diseases.

According to one of the study’s authors, Cynthia Kenyan, “If you take people with Alzheimer’s and look at their aggregates, there are many other proteins in the clump that no one has ever paid much attention to. It turns out that about half of these proteins are aggregating proteins that become insoluble as a normal part of aging.”

There are several hundred proteins involved in this system, many associated with cell growth.

The paper, published in the Open Access journal PLoS Biology, is downloadable here.

David, D., Ollikainen, N., Trinidad, J., Cary, M., Burlingame, A., & Kenyon, C. (2010). Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans PLoS Biology, 8 (8) DOI: 10.1371/journal.pbio.1000450