More insight into metformin's beneficial effects on diabetes, aging, and several diseases.

A group at McMaster University has shown an effect of the diabetes drug metformin beyond its suppression of liver glucose production that might partially explain its beneficial effects on aging and a number of diverse diseases such as cognitive disorders, cancer and cardiovascular disease. (There are currently over 1,500 registered clinical trials to test the effects of metformin in aging and different diseases.) It induces the expression and secretion of growth differentiating factor 15 (GDF15) in mouse liver cells, a protein known to suppress appetite and cause weight loss.

I'm sorely tempted to try to get myself a prescription for the stuff! Here is the technical abstract of the article:

Metformin is the most commonly prescribed medication for type 2 diabetes, owing to its glucose-lowering effects, which are mediated through the suppression of hepatic glucose production (reviewed in refs. 1,2,3). However, in addition to its effects on the liver, metformin reduces appetite and in preclinical models exerts beneficial effects on ageing and a number of diverse diseases (for example, cognitive disorders, cancer, cardiovascular disease) through mechanisms that are not fully understood1,2,3. Given the high concentration of metformin in the liver and its many beneficial effects beyond glycemic control, we reasoned that metformin may increase the secretion of a hepatocyte-derived endocrine factor that communicates with the central nervous system4. Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3). In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice. An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin. Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.

Heritable gaps between chronological age and brain age are increased in common brain disorders.

Kaufmann et al. have used machine learning on s large dataset to estimate robust estimation of individual biological brain ages on the basis of structural brain imaging features. The deviation between brain age and chronological age — termed the brain age gap — appears to be a promising marker of brain health. It was largest in schizophrenia, multiple sclerosis, dementia, and bipolar spectrum disorder. The authors also assessed the overlap between the genetic underpinnings of brain age gap and common brain disorders. The bottom line conclusion (from a very extensive and complex analysis) is that common brain disorders are associated with heritable patterns of apparent aging of the brain Their abstract:

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3–96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

Same-Sex behavior in animals - a new view.

Monk et al. offer a fresh perspective on the "problem" of how same-sex sexual behavior could have evolved. It is a problem only if different-sex sexual behavior is the baseline condition for animals, from which single-sex behavior has evolved. The authors suggest that same-sex behavior is bound up in the very origins of animal sex. It hasn’t had to continually re-evolve: It’s always been there. The arguments of Monk and collaborators are summarized in a review by Elbein:

Instead of wondering why same-sex behavior had independently evolved in so many species, Ms. Monk and her colleagues suggest that it may have been present in the oldest parts of the animal family tree. The earliest sexually reproducing animals may have mated with any other individual they came across, regardless of sex. Such reproductive strategies are still practiced today by hermaphroditic species, like snails, and species that don’t appear to differentiate, like sea urchins.

Over time, Ms. Monk said, sexual signals evolved — different sizes, colors, anatomical features and behaviors — allowing different sexes to more accurately target each other for reproduction. But same-sex behavior continued in some organisms, leading to diverse sexual behaviors and strategies across the animal kingdom. And while same-sex behavior may grant some evolutionary benefits, an ancient origin would mean those benefits weren’t required for it to exist.

But how has same-sex behavior stuck around? The answer may be that such behaviors aren’t as evolutionarily costly as assumed. Traditionally, Ms. Monk said, any mating behavior that doesn’t produce young is seen as a waste. But animal behavior often doesn’t fit neatly into an economic accounting of costs and benefits.

Here is the abstract of Monk et al.:

Same-sex sexual behaviour (SSB) has been recorded in over 1,500 animal species with a widespread distribution across most major clades. Evolutionary biologists have long sought to uncover the adaptive origins of ‘homosexual behaviour’ in an attempt to resolve this apparent Darwinian paradox: how has SSB repeatedly evolved and persisted despite its presumed fitness costs? This question implicitly assumes that ‘heterosexual’ or exclusive different-sex sexual behaviour (DSB) is the baseline condition for animals, from which SSB has evolved. We question the idea that SSB necessarily presents an evolutionary conundrum, and suggest that the literature includes unchecked assumptions regarding the costs, benefits and origins of SSB. Instead, we offer an alternative null hypothesis for the evolutionary origin of SSB that, through a subtle shift in perspective, moves away from the expectation that the origin and maintenance of SSB is a problem in need of a solution. We argue that the frequently implicit assumption of DSB as ancestral has not been rigorously examined, and instead hypothesize an ancestral condition of indiscriminate sexual behaviours directed towards all sexes. By shifting the lens through which we study animal sexual behaviour, we can more fruitfully examine the evolutionary history of diverse sexual strategies.

Something in the way we move.

Gretchen Reynolds points to work by Hug et al. suggesting that each of us has a unique muscle activation signature that can be revealed during walking and pedaling. Understanding movement patterns could help in improving and refining robotics, prosthetics, physical therapy and personalized exercise programs. On the darker side, a Chinese company (Watrix) is using computer vision to to enhance the recognition of individuals in crowds by their walking postures:

...its gait recognition solution “Shuidi Shenjian” ... will enable security departments to quickly search and recognize identities by their body shape and walking posture. The company notes that this product is highly effective when targets walk from a long distance or in weak light, cover their faces or wear different clothes, and would be a great supplement to current computer vision products.

Here is the complete abstract from Hug et al.:

Although it is known that the muscle activation patterns used to produce even simple movements can vary between individuals, these differences have not been considered to prove the existence of individual muscle activation strategies (or signatures). We used a machine learning approach (support vector machine) to test the hypothesis that each individual has unique muscle activation signatures. Eighty participants performed a series of pedaling and gait tasks, and 53 of these participants performed a second experimental session on a subsequent day. Myoelectrical activity was measured from eight muscles: vastus lateralis and medialis, rectus femoris, gastrocnemius lateralis and medialis, soleus, tibialis anterior, and biceps femoris-long head. The classification task involved separating data into training and testing sets. For the within-day classification, each pedaling/gait cycle was tested using the classifier, which had been trained on the remaining cycles. For the between-day classification, each cycle from day 2 was tested using the classifier, which had been trained on the cycles from day 1. When considering all eight muscles, the activation profiles were assigned to the corresponding individuals with a classification rate of up to 99.28% (2,353/2,370 cycles) and 91.22% (1,341/1,470 cycles) for the within-day and between-day classification, respectively. When considering the within-day classification, a combination of two muscles was sufficient to obtain a classification rate >80% for both pedaling and gait. When considering between-day classification, a combination of four to five muscles was sufficient to obtain a classification rate >80% for pedaling and gait. These results demonstrate that strategies not only vary between individuals, as is often assumed, but are unique to each individual.

Rival theories of consciousness being tested by large project.

In the first phase of a $20 million dollar project, six laboratories are going to run experiments with more than 500 participants to test two of the primary theories of consciousness:

The first two contenders are the global workspace theory (GWT), championed by Stanislas Dehaene of the Collège de France in Paris, and the integrated information theory (IIT), proposed by Giulio Tononi of the Uni-versity of Wisconsin in Madison. The GWT says the brain’s prefrontal cortex, which con-trols higher order cognitive processes like decision-making, acts as a central computer that collects and prioritizes information from sensory input. It then broadcasts the infor-mation to other parts of the brain that carry out tasks. Dehaene thinks this selection pro-cess is what we perceive as consciousness. By contrast, the IIT proposes that conscious-ness arises from the interconnectedness of brain networks. The more neurons interact with one another, the more a being feels conscious—even without sensory input. IIT proponents suspect this process occurs in the back of the brain, where neurons con-nect in a gridlike structure...Tononi and Dehaene have agreed to pa-rameters for the experiments and have reg-istered their predictions. To avoid conflicts of interest, the scientists will neither collect nor interpret the data. If the results appear to disprove one theory, each has agreed to admit he was wrong—at least to some extent

The labs, in the United States, Germany, the United Kingdom, and China, will use three techniques to record brain activity as volun-teers perform consciousness-related tasks: functional magnetic resonance imaging, electroencephalography, and electrocortico-graphy (a form of EEG done during brain sur-gery, in which electrodes are placed directly on the brain). In one experiment, research-ers will measure the brain’s response when a person becomes aware of an image. The GWT predicts the front of the brain will suddenly become active, whereas the IIT says the back of the brain will be consistently active.

The real cost of texting and tweeting.

Agnes Callard, an associate professor of philosophy at the University of Chicago, crystallizes some fascinating points in an NYTimes Op-Ed piece. She wonders why she broadcasts the details of her daily life on twitter...some clips:

To allow others to think about us in whatever way they feel like — perhaps to laugh at us, perhaps to dismiss us — is a huge loss of control. So why do we allow it? What is the attraction of it? I think that it’s the increase in control we get in return. Social media has enabled the Great Control Swap. And it is happening right now, beneath our notice.

The first baby step toward the Great Swap was the shift from phone calls to texts. A phone interaction requires participants to be “on the same time,” which entails negotiations over entrance into and exit from the conversation...A text or email interaction, by contrast, liberates the parties so that each may operate on their own time. But the cost comes in another form of control: data....text-based communication requires stationary words...they leave a trail.

We understood from the start that this form of socializing — like an affair without physical contact — was shallower than the other, more demanding kind. We were prepared to accept that trade-off, but failed to grasp that we were trading away more than depth. We were also trading away a kind of control.

All of us have a desire to connect, to be seen. But we live in a world that is starting to allow us to satisfy that desire without feeling the common-sense moral strictures that have traditionally governed human relationships. We can engage without obligation, without boredom and, most importantly, without subjecting our attention to the command of another. On Twitter, I’m never obligated to listen through to the end of someone’s story.

The immense appeal of this free-form socializing lies in the way it makes one a master of one’s own time — but it cannot happen without a place. All that data has to sit somewhere so that people can freely access it whenever they wish. Data storage is the loss of control by which we secure social control: Facebook is our faithless mistress’s leaky inbox.

When we alienate our identities as text data, and put that data “out there” to be read by anyone who wanders by, we are putting ourselves into the interpretive hands of those who have no bonds or obligations or agreements with us, people with whom we are, quite literally, prevented from seeing “eye to eye.” People we cannot trust.

The Great Control Swap buys us control over the logistics of our interactions at the cost of interpretive control over the content of those interactions. Our words have lost their wings, and fallen to the ground as data.

Cognitive and noncognitive predictors of success.

An interesting bit of work from Duckworth et al.

When predicting success, how important are personal attributes other than cognitive ability? To address this question, we capitalized on a full decade of prospective, longitudinal data from n = 11,258 cadets entering training at the US Military Academy at West Point. Prior to training, cognitive ability was negatively correlated with both physical ability and grit. Cognitive ability emerged as the strongest predictor of academic and military grades, but noncognitive attributes were more prognostic of other achievement outcomes, including successful completion of initiation training and 4-y graduation. We conclude that noncognitive aspects of human capital deserve greater attention from both scientists and practitioners interested in predicting real-world success.

How trance states might have forged human societies

I want to pass on a series of clips I have made for my own use from an intriguing article by Mark Vernon in Aeon:

With anatomically modern humans comes culture in a way that had never happened before. And from that culture came religion, with various proposals to map the hows and whys of its emergence. Until recently, the proposals fell into two broad groups – ‘big gods’ theories and ‘false agency’ hypotheses. Big gods theories envisage religion as conjuring up punishing deities. These disciplining gods provided social bonding by telling individuals that wrongdoing incurs massive costs. The problem is that big gods are not a universal feature of religions and, if they are present, they seem correlated to big societies not causes of them. False agency hypotheses...assume that our forebears were jumpy and superstitious: they thought that a shrub swayed because of a spirit not the wind; and they were easily fooled, though their mistakes were evolutionarily advantageous because, on occasion, the swaying was caused by a predator. The false agency hypothesis has been tested and disconfirmed across many experiments.

...there is a need for a new idea, and coming to the fore now is an old one revisited...The explanation is resurfacing in what can be called the trance theory of religious origins, which proposes that our paleolithic ancestors hit on effervescence upon finding that they could induce altered states of consciousness...Effervescence is generated when humans come together to make music or perform rituals, an experience that lingers when the ceremonies are over. The suggestion, therefore, is that collective experiences that are religious or religious-like unify groups and create the energy to sustain them.

Research to test and develop this idea is underway in a multidisciplinary team led by Robin Dunbar at the University of Oxford. The approach appeals to him, in part, because it seems to capture a crucial aspect of religious phenomena missing in suggestions about punishing gods or dangerous spirits. It is not about the fine details of theology, but is about the raw feelings of experience...this raw-feelings element has a transcendental mystical component – something that is only fully experienced in trance states...this sense of transcendence and other worlds is present at some level in almost all forms of religious experience.

...there’s evidence that monkeys and apes experience the antecedents to ecstasy because they seem to experience wonder...a few hundred thousand years ago, archaic humans took a step that ramped up this capacity. They started deliberately to make music, dance and sing. When the synchronised and collective nature of these practices became sufficiently intense, individuals likely entered trance states in which they experienced not only this-worldly splendour but otherworldly intrigue... What you might call religiosity was born. It stuck partly because it also helped to ease tensions and bond groups, via the endorphin surges produced in trance states. In other words, altered states proved evolutionarily advantageous: the awoken human desire for ecstasy simultaneously prompted a social revolution because it meant that social groups could grow to much larger sizes via the shared intensity of heightened experiences.

The trance hypothesis...rests on the rituals that produce peak experiences, which means it doesn’t require speculating about what ancient people did or didn’t believe about spirits and gods...Asking when religion evolved is not a good question because religion is more than one thing...asking when the various elements such as supernatural agents and moral obligations started to coalesce together is a better question. And they invariably start to coalesce around rituals.

...when villages and then towns appear...new techniques for managing social pressures are required...religious systems (Doctrinal religions) that include specialists such as priests and impressive constructions we’d call temples and/or domestic house-based shrines...sustain the prosocial effects of earlier types of religiosity for groups that are now growing very large indeed...a tension .. arises when religious experiences are institutionalised....what’s on offer is somewhat thinner than experiences gained in the immersive rites that precipitate altered states. Encountering spirit entities directly in a dance or chase is not the same as the uplift offered by a monumental building.

...religions are caught between the Scylla of socially useful but potentially dreary religious rites and the Charybdis of altered states that are intrinsically exciting but socially disruptive. It’s why they bring bloody conflicts as well as social goods. This way of putting it highlights another feature of the trance theory. It interweaves two levels of explanation: one focused on the allure of spiritual vitality; the other on practical needs.

..science cannot decide whether the claims of any one religion are true. But the new theory still makes quite a strong claim, which brings me back to the role of the supernatural, transcendence and religious gods that today’s secularists seem inclined to sideline. If the science cannot confirm convictions about any divine revelations received, it does lend credence to the reasonableness, even necessity, of having them. Where the big gods and false agency hypotheses seemed inherently sniffy about human religiosity, the trance hypothesis positively values it...The trance hypothesis is neutral about the truth claims of religions whether you believe or don’t, though it does suggest that transcendent states of mind are meaningful to human beings and can evolve into religious systems of belief.

And in this final observation there is, perhaps, some good news for us, whether we’re religious or not. It’s often said that many of today’s troubles, from divisive political debates to spats on social media, are due to our tribal nature. It’s added, somewhat fatalistically, that deep within our evolutionary past is the tendency to identify with one group and demonise another. We are destined to be at war, culturally or otherwise. But if the trance theory is true, it shows that the evolutionary tendency to be tribal rests on an evolutionary taste for that which surpasses tribal experience – the transcendence that humans glimpsed in altered states of mind that enabled them to form tribes to start with.

If we long to belong, we also long to be in touch with ‘the more’, as the great pioneer of the study of religious experiences William James called it. That more will be envisaged in numerous ways. But it might help us by prompting new visions that exceed our herd instincts and binary thinking, and ease social tensions. If it helped our ancestors to survive, why would we think we are any different?

Evidence for premature aging caused by insufficient sleep.

I have come to realize in the past year or so that my physical and mental robustness require getting at least seven, and preferably eight, hours of sleep every night. Thus I was intrigued by finding an extensive and well documented study by Teo et al. (open source) showing that telomeres, sequences of DNA on the end of chromosomes taken as a marker of biological aging, are, on average, 356 base pairs shorter in study participants who slept for fewer than five hours per night than in those who slept for seven hours. They found that sleep metrics were reported more accurately by wearable fitness trackers than by self report. Here is the abstract of their article, titled "Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging."

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST; they included age, gender, occupation and alcohol consumption. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with cardiovascular disease risk markers such as body mass index and waist circumference, whereas self-reported measures were not. Using wearable-derived TST, we showed that insufficient sleep was associated with premature telomere attrition. Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.

A "Department of the Attention Economy"

Popping up on my daily input stream (in this case the Google News aggregator - which knows more that I do about what I might like to see) is a CNN business perspective titled "Andrew Yang: As president, I will establish a Department of the Attention Economy." It is an idea that I wish some of the more likely democratic nominees would take up.

The article immediately caught my attention, because faced with the immense array of input text and video streams competing for my attention I feel, as I suspect many MindBlog readers do, like one of the dogs in Martin Seligman's classic learned helplessness experiments whose stress and immune systems eventually are compromised by uncertainty. For entertainment should I be subscribing to Netflix, Hulu, Amazon Prime, Disney+, YouTube +, Apple TV+, CBS All Access, AcornTV, Britbox, Shudder, YouTbue, Facebook Watch, Tubi, etc.? For news, there are too many options to even begin to list them. Apart from my own qualms about using Google as a prosthesis (Blogger, Google Docs, Calendar, Mail, etc.), I look at how my 5 and 7 year old grandsons' lives are potentially compromised by the amount of free time they spend on digital inputs rather than playing outside with friends.

Clips rom Yang's article:

...technology is addictive and damaging the mental health of our children. Research shows that too much time spent on social media increases stress, anxiety, depression and feelings of isolation. Other studies have found that extended screen time can negatively affect sleep...As president, I will establish a Department of the Attention Economy that will work with tech companies and implement regulations that curb the negative effects of smartphones and social media.

A few of his suggestions:

We can start by curbing design features that maximize screen time, such as removing autoplay video and capping recommendations for videos, articles and posts for each user each day. Platforms can also use deep-learning algorithms to determine whether a user is a child, and then explore capping the user's screen hours per day.

Design features that encourage social validation should also be removed. Instagram is leading the way by testing hiding likes on the posts of some users. That's a step in the right direction and it should be implemented as soon as possible. In addition, the number of followers a person has on social media should be hidden too, as it represents a false equivalence with a person's social standing.

Another area that deserves attention is the content our kids consume. When I was growing up, television time meant morning cartoons and after-school specials. Rules and standards should be established to protect kids from graphic content and violent imagery. Subsequently, these regulations would also incentivize the production of high-quality content and positive programming.

It shouldn't stop there. Parents have a major role to play — and they want to — but they could use some help. Companies should be required to provide parents with guidance on kid-healthy content (similar to the rating system for TV or movies), and parents should easily be able to monitor content and screen time for children.

Social class is revealed by brief clips of speech.

Kraus et al. - a collective modern version of Professor Henry Higgins in George Bernard Shaw's play Pygmalion - offer a detailed analytic update on how social class is reproduced through subtle cues expressed in brief speech. Here is their abstract:

Economic inequality is at its highest point on record and is linked to poorer health and well-being across countries. The forces that perpetuate inequality continue to be studied, and here we examine how a person’s position within the economic hierarchy, their social class, is accurately perceived and reproduced by mundane patterns embedded in brief speech. Studies 1 through 4 examined the extent that people accurately perceive social class based on brief speech patterns. We find that brief speech spoken out of context is sufficient to allow respondents to discern the social class of speakers at levels above chance accuracy, that adherence to both digital and subjective standards for English is associated with higher perceived and actual social class of speakers, and that pronunciation cues in speech communicate social class over and above speech content. In study 5, we find that people with prior hiring experience use speech patterns in preinterview conversations to judge the fit, competence, starting salary, and signing bonus of prospective job candidates in ways that bias the process in favor of applicants of higher social class. Overall, this research provides evidence for the stratification of common speech and its role in both shaping perceiver judgments and perpetuating inequality during the briefest interactions.

Here is a sample explanatory clip from their results section:

A total of 229 perceivers were asked to listen to the speech of 27 unique speakers whose utterances were collected as part of a larger sample of 189 speakers through the International Dialects of English Archive (IDEA). These 27 speakers varied in terms of age, race, gender, and social class, which we measured in the present study in terms of high school or college degree attainment. Our sample of perceivers listened to 7 words spoken by each of the speakers presented consecutively and randomly without any other accompanying speech and answered “Yes” or “No” to 4 questions: “Is this person a college graduate/woman/young/white?” Participants answered these 4 questions in a randomized order, and we calculated the proportion of correct responses for each question...

Explaining the puzzle of human diversity in the Christian world

Fascinating work by Schulz et al. is reviewed by both Gelfand and also Zauzmer. Schultz et al. show how the specific practices of Medieval Christianity can in part explain widespread variation in human psychology around the world.

From Zauzmer:

The story begins with kinship networks — the tribes and clans of densely connected, insular groups of relatives who formed most human societies before medieval times. Catholic Church teachings disrupted those networks, in large part by vehemently prohibiting marriage between relatives (which had been de rigeur), and eventually provoked a wholesale transformation of communities, changing the norm from large clans into small, monogamous nuclear families.

The team analyzed Vatican records to document the extent of a country or region’s exposure to Catholicism before the year 1500, and found that longer exposure to Catholicism correlated with low measures of kinship intensity in the modern era, including low rates of cousins marrying each other. Both measures correlated with psychology, the researchers found by looking at 24 different psychological traits of people in different cultures: Countries exposed to Catholicism early have citizens today who exhibit qualities such as being more individualistic and independent, and being more trusting of strangers.

From Gelfand:

...the authors found that both longer exposure to the Western Church and weaker kinship intensity (which were negatively related, as expected) were associated with greater individualism and independence, less conformity and obedience, and greater prosociality toward strangers—relationships that mostly held when controlling for a range of geographic variables. The results were replicated across 440 regions in 36 European countries: Longer exposure to the Western Church was generally associated with the same WEIRD (Western, Educated, Industrialized, Rich and Democratic) psychological shifts, even when controlling for alternate explanations (e.g., the influence of Roman political institutions, schooling, migration).

New work on how and why we sleep.

The fact that I'm finding the quality of my sleep to be central to my robustness and well-being makes me want to pass on descriptions of four pieces of work described in recent issues of Science Magazine, work showing housekeeping changes in our brains happening while we sleep, changes whose disruption by sleep deprivation has debilitating consequences. Fultz et al. show that deep sleep drives brain fluid oscillations that may facilitate communication between fluid compartments and clearance of waste products. Todorova and Zugaro show that spikes during delta waves of sleep (widespread cortical silence) support memory consolidation. Brüning et al. find in the mouse brain that half of the 2000 synaptic phosphoproteins quantified show changes with daily activity-rest cycles. Sleep deprivation abolishes nearly all (98%) of these phosphorylation cycles at synapses. Noya et al. find a sleep-wake cycle in which transcripts and proteins associated with synaptic signaling accumulate before the active phase (dusk for nocturnal mice), whereas messenger RNAs and proteins associated with metabolism and translation accumulate before the resting phase.

Why we can't tell the truth about aging.

I've enjoyed reading the New Yorker essay by Arthur Krystal titled "Why we can't tell the truth about aging," which points to and discusses numerous recent (as well as a few ancient) books on aging. Here is a selection of rearranged small clips from the article.

Average life expectancy was indeed a sorry number for the greater part of history (for Americans born as late as 1900, it wasn’t even fifty), which may be one reason that people didn’t write books about aging: there weren’t enough old folks around to sample them. But now that more people on the planet are over sixty-five than under five, an army of readers stands waiting to learn what old age has in store.

Now that we’re living longer, we have the time to write books about living longe...The library on old age has grown so voluminous that the fifty million Americans over the age of sixty-five could spend the rest of their lives reading such books, even as lusty retirees and power-lifting septuagenarians turn out new ones.

Our senior years are evidently a time to celebrate ourselves and the wonderful things to come: travelling, volunteering, canoodling, acquiring new skills, and so on. No one, it seems, wants to disparage old age...we get cheerful tidings...chatty accounts meant to reassure us that getting old just means that we have to work harder at staying young...authors aren’t blind to the perils of aging; they just prefer to see the upside. All maintain that seniors are more comfortable in their own skins.

There is, of course, a chance that you may be happier at eighty than you were at twenty or forty, but you’re going to feel much worse. I know this because two recent books provide a sobering look at what happens to the human body as the years pile up. Elizabeth Blackburn and Elissa Epel’s “The Telomere Effect: Living Younger, Healthier, Longer” and Sue Armstrong’s “Borrowed Time: The Science of How and Why We Age” describe what is essentially a messy business.

Basically, most cells divide and replicate some fifty-plus times before becoming senescent. Not nearly as inactive as the name suggests, senescent cells contribute to chronic inflammation and interfere with protective collagens...The so-called epigenetic clock shows our DNA getting gummed up, age-related mitochondrial mutations reducing the cells’ ability to generate energy, and our immune system slowly growing less efficient. Bones weaken, eyes strain, hearts flag. Bladders empty too often, bowels not often enough, and toxic proteins build up in the brain to form the plaque and the spaghetti-like tangles that are associated with Alzheimer’s disease. Not surprisingly, sixty-eight per cent of Medicare beneficiaries today have multiple chronic conditions. Not a lot of grace, force, or fascination in that.

In short, the optimistic narrative of pro-aging writers doesn’t line up with the dark story told by the human body. But maybe that’s not the point. “There is only one solution if old age is not to be an absurd parody of our former life,” Simone de Beauvoir wrote in her expansive 1970 study “The Coming of Age,” “and that is to go on pursuing ends that give our existence a meaning—devotion to individuals, to groups, or to causes—social, political, intellectual, or creative work.”

One would, of course, like to approach old age with grace and fortitude, but old age makes it difficult. Those who feel that it’s a welcome respite from the passions, anxieties, and troubles of youth or middle age are either very lucky or toweringly reasonable. Why rail against the inevitable—what good will it do? None at all. Complaining is both pointless and unseemly. Existence itself may be pointless and unseemly.

We should all make peace with aging. And so my hat is off to Dr. Oliver Sacks, who chose to regard old age as “a time of leisure and freedom, freed from the factitious urgencies of earlier days, free to explore whatever I wish, and to bind the thoughts and feelings of a lifetime together.”

World wide movement of people into cities is degrading the human microbiome

From the Oct. 25 issue of Science Magazine:

Sonnenburg and Sonnenburg review how the shift of recent generations from rural, outdoor environments to urbanized and industrialized settings has profoundly affected our biology and health. The signals of change are seen most strikingly in the reduction of commensal microbial taxa and loss of their metabolic functions. The extirpation of human commensals is a result of bombardment by new chemicals, foodstuffs, sanitation, and medical practices. For most people, sanitation and readily available food have been beneficial, but have we now reached a tipping point? How do we “conserve” our beneficial symbionts and keep the pathogens at bay?

Here is their abstract:

The human body is an ecosystem that is home to a complex array of microbes known as the microbiome or microbiota. This ecosystem plays an important role in human health, but as a result of recent lifestyle changes occurring around the planet, whole populations are seeing a major shift in their gut microbiota. Measures meant to kill or limit exposure to pathogenic microbes, such as antibiotics and sanitation, combined with other factors such as processed food, have had unintended consequences for the human microbial ecosystem, including changes that may be difficult to reverse. Microbiota alteration and the accompanying loss of certain functional attributes might result in the microbial communities of people living in industrialized societies being suboptimal for human health. As macroecologists, conservationists, and climate scientists race to document, understand, predict, and delay global changes in our wider environment, microbiota scientists may benefit by using analogous approaches to study and protect our intimate microbial ecosystems.

How human breeding has changed dogs’ brains

Hecht et al. have identified brain networks in dogs related to behavioral specializations roughly corresponding to sight hunting, scent hunting, guarding, and companionship. Here is their detailed abstract:

Humans have bred different lineages of domestic dogs for different tasks such as hunting, herding, guarding, or companionship. These behavioral differences must be the result of underlying neural differences, but surprisingly, this topic has gone largely unexplored. The current study examined whether and how selective breeding by humans has altered the gross organization of the brain in dogs. We assessed regional volumetric variation in MRI studies of 62 male and female dogs of 33 breeds. Neuroanatomical variation is plainly visible across breeds. This variation is distributed nonrandomly across the brain. A whole-brain, data-driven independent components analysis established that specific regional subnetworks covary significantly with each other. Variation in these networks is not simply the result of variation in total brain size, total body size, or skull shape. Furthermore, the anatomy of these networks correlates significantly with different behavioral specialization(s) such as sight hunting, scent hunting, guarding, and companionship. Importantly, a phylogenetic analysis revealed that most change has occurred in the terminal branches of the dog phylogenetic tree, indicating strong, recent selection in individual breeds. Together, these results establish that brain anatomy varies significantly in dogs, likely due to human-applied selection for behavior.

A triple drug combination increases lifespan by 48%

In Drosophila flies, to be sure, but the nutrient sensing pathways that are the target of the drugs are common to all animals. Here is the abstract from open source article by Castillo-!uan et al.:

Increasing life expectancy is causing the prevalence of age-related diseases to rise, and there is an urgent need for new strategies to improve health at older ages. Reduced activity of insulin/insulin-like growth factor signaling (IIS) and mechanistic target of rapamycin (mTOR) nutrient-sensing signaling network can extend lifespan and improve health during aging in diverse organisms. However, the extensive feedback in this network and adverse side effects of inhibition imply that simultaneous targeting of specific effectors in the network may most effectively combat the effects of aging. We show that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, the mTOR complex 1 (mTORC1) inhibitor rapamycin, and the glycogen synthase kinase-3 (GSK-3) inhibitor lithium act additively to increase longevity in Drosophila. Remarkably, the triple drug combination increased lifespan by 48%. Furthermore, the combination of lithium with rapamycin cancelled the latter’s effects on lipid metabolism. In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health.

Skill development - the intelligence vs. practice debate reframed

Vaci et al. note that what is often overlooked in the nature vs. nurture debate is the fact that both factors interact with each other:

The relative importance of different factors in the development of human skills has been extensively discussed. Research on expertise indicates that focused practice may be the sole determinant of skill, while intelligence researchers underline the relative importance of abilities at even the highest level of skill. There is indeed a large body of research that acknowledges the role of both factors in skill development and retention. It is, however, unknown how intelligence and practice come together to enable the acquisition and retention of complex skills across the life span. Instead of focusing on the 2 factors, intelligence and practice, in isolation, here we look at their interplay throughout development. In a longitudinal study that tracked chess players throughout their careers, we show that both intelligence and practice positively affect the acquisition and retention of chess skill. Importantly, the nonlinear interaction between the 2 factors revealed that more intelligent individuals benefited more from practice. With the same amount of practice, they acquired chess skill more quickly than less intelligent players, reached a higher peak performance, and arrested decline in older age. Our research demonstrates the futility of scrutinizing the relative importance of highly intertwined factors in human development.

The miracle cure - just move

A summary from the editor of the British Medical Journal of work by Ekelund et. al.:

As miracle cures are hard to come by, any claims that a treatment is 100% safe and effective must always be viewed with intense scepticism. There is perhaps one exception. Physical activity has been called a miracle cure by no less a body than the Academy of Medical Sciences (http://bit.ly/2lTqDvc); and, like those who avail themselves of it, the supporting science grows stronger by the day. The BMJ recently published a systematic review showing a clear dose-response relation between physical activity and all cause mortality (doi:10.1136/bmj.l4570). The authors concluded that any level of activity is better than none, and more is better still, a message recently encapsulated in the updated guidelines from the UK’s chief medical officers (doi:10.1136/bmj.l5470).

The statement from the authors on their analysis of numerous studies:

We conducted a harmonised meta-analysis to examine the association between accelerometer measured physical activity and sedentary time and all cause mortality. Specifically, we examined the dose-response relations of total physical activity, different intensities of physical activity (light, low light, high light, moderate to vigorous, and vigorous) and sedentary time and all cause mortality.

Feeling grateful - a shortcut to virtuous behavior.

Psychologist David DeSteno, in an Aeon essay, summarizes his experiments suggesting that moving towards a more virtuous life might accomplished by simply cultivating gratitude, a more simple route than through deep deliberation on noble qualities such as honesty and generosity. Subjects were asked to report the results of a coin toss in which heads yielded a larger financial reward than tails. The coins were rigged to always come up tails.

The percentage of cheaters fell by half (from almost 49 per cent to 27 per cent) among those who had just recalled a time when they felt grateful, compared with those who described a time when they felt happy or no particular emotion at all.

They then did a second experiment that..

...had two key differences. First, the coin flip determined whether any given participant would have to complete an enjoyable 10-minute task or a difficult 45-minute one. Second, we led participants to believe that the next person to come would be assigned to complete whichever task remained.

In deciding to cheat by reporting that the virtual coin flip came up heads, people were giving themselves a much shorter and more enjoyable task, but in so doing, were also unfairly dooming another person to a more onerous task.

As one might imagine, the overall frequency of cheating was lower. Nonetheless, gratitude worked in the exact same way. Whereas 17 per cent of people cheated when feeling neutral or happy, only 2 per cent cheated when feeling grateful.

The empirical literature shows a similar influence of gratitude on other virtues. People feeling grateful are more likely to help others who request assistance, to divide their profits in a more egalitarian way, to be loyal even at cost to themselves, to be less materialistic, and even to exercise as opposed to loafing.