Aging Aesthetics Reversed in Mice

Mice are similar enough to humans to make this interesting.

Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?

Keshav Singh, Ph.D., and colleagues have done just that, in a mouse model developed at the University of Alabama at Birmingham. When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.

“To our knowledge, this observation is unprecedented,” said Singh, a professor of genetics in the UAB School of Medicine.

Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive.

In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders and cancer.

“This mouse model,” Singh said, “should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of aging-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.”

The mutation in the mouse model is induced when the antibiotic doxycycline is added to the food or drinking water. This causes depletion of mitochondrial DNA because the enzyme to replicate the DNA becomes inactive.

[…]

Reversal of the mutation restored mitochondrial function, as well as the skin and hair pathology. This showed that mitochondria are reversible regulators of skin aging and loss of hair, an observation that Singh calls “surprising.”

Research: Everyone has Unique Brain Anatomy

Apparently this wasn’t thought much 30 years ago. It is also a bit surprising that some of the differences are driven primarily by repeated experiences.

Like with fingerprints, no two people have the same brain anatomy, a study by researchers of the University of Zurich has shown. This uniqueness is the result of a combination of genetic factors and individual life experiences.

The fingerprint is unique in every individual: As no two fingerprints are the same, they have become the go-to method of identity verification for police, immigration authorities and smartphone producers alike. But what about the central switchboard inside our heads? Is it possible to find out who a brain belongs to from certain anatomical features? This is the question posed by the group working with Lutz Jäncke, UZH professor of neuropsychology. In earlier studies, Jäncke had already been able to demonstrate that individual experiences and life circumstances influence the anatomy of the brain.

Experiences make their mark on the brain

Professional musicians, golfers or chess players, for example, have particular characteristics in the regions of the brain which they use the most for their skilled activity. However, events of shorter duration can also leave behind traces in the brain: If, for example, the right arm is kept still for two weeks, the thickness of the brain’s cortex in the areas responsible for controlling the immobilized arm is reduced. “We suspected that those experiences having an effect on the brain interact with the genetic make-up so that over the course of years every person develops a completely individual brain anatomy,” explains Jäncke.

Magnetic resonance imaging provides basis for calculations

To investigate their hypothesis, Jäncke and his research team examined the brains of nearly 200 healthy older people using magnetic resonance imaging three times over a period of two years. Over 450 brain anatomical features were assessed, including very general ones such as total volume of the brain, thickness of the cortex, and volumes of grey and white matter. For each of the 191 people, the researchers were able to identify an individual combination of specific brain anatomical characteristics, whereby the identification accuracy, even for the very general brain anatomical characteristics, was over 90 percent.

Combination of circumstances and genetics

“With our study we were able to confirm that the structure of people’s brains is very individual,” says Lutz Jäncke on the findings. “The combination of genetic and non-genetic influences clearly affects not only the functioning of the brain, but also its anatomy.” The replacement of fingerprint sensors with MRI scans in the future is unlikely, however. MRIs are too expensive and time-consuming in comparison to the proven and simple method of taking fingerprints.

Progress in neuroscience

An important aspect of the study’s findings for Jäncke is that they reflect the great developments made in the field in recent years: “Just 30 years ago we thought that the human brain had few or no individual characteristics. Personal identification through brain anatomical characteristics was unimaginable.”

Boosting Serotonin Can Speed Learning

I’m sure this research has more implications than currently realized.

Serotonin is thought to mediate communications between neural cells and play an essential role in functional, and dysfunctional, cognition. For a long time, serotonin has been recognized as a major target of antidepressants (selective-serotonin-reuptake-inhibitor (SSRIs) that are used to treat various psychiatric conditions, such as depression, obsessive-compulsive-disorder and forms of anxiety. However, serotonin in humans, and other animals, is associated with a bewildering variety of aspects of cognition and decision-making, including punishment, reward and patience.

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In the experiments, mice were trained to choose one of the two targets to receive water rewards. Mice continually had to learn which of the targets was more rewarding, as the reward rates changed without warning. Crucially, sometimes serotonin release in the brain was temporarily boosted in mice with genetically modified serotonin neurons by a technique called optogenetics, allowing the effects of serotonin on learning to be assessed.

Iigaya built a computational account of mice behaviour based on reinforcement learning principles, which are widely used in machine-learning and AI. Iigaya found that the learning rate, i.e. how fast the modelled mice learn, was modulated by serotonin stimulation. He compared trials with and without stimulation of serotonin neurons, and observed that the learning rate was significantly faster when stimulation was delivered, meaning that boosting serotonin sped up learning in mice.

[…]

The authors conclude: “Our results suggest that serotonin boosts [brain] plasticity by influencing the rate of learning. This resonates, for instance, with the fact that treatment with an SSRI can be more effective when combined with so-called cognitive behavioral therapy, which encourages the breaking of habits in patients.”

Substantial clinical research shows that SSRI treatment is often most effective if combined with cognitive-behavioural-therapy (CBT). The goal of CBT is to change maladaptive thinking and behaviour actively, through sessions that are designed for patients to (re)learn their way to think and behave. However, scientists have had limited understanding of how and why SSRI and CBT work together for treatments. The new findings point to a possible functional link between the two, with serotonin boosting the learning inherent to CBT, providing clues as to one of the roles that this neuromodulator plays in the treatment of psychiatric disorders.

Allowing Employees More Autonomy Improves Their Performance

More worker autonomy is shown globally to increase worker productivity. It’s one of the strongest arguments in favor of ditching the undemocratic top-down structure of capitalist enterprises in favor of using democratically run worker cooperatives. At the very least, countries could adopt Germany’s policies of co-determination, which gives German workers increased participation in managing companies.

Managers who encourage staff to take more control over their workflow by putting them in the driver’s seat find themselves with more competent and connected teams with motivated, engaged, high-performing and loyal employees, research by the University of Melbourne shows.

Leaders who employ a style known as autonomously supportive, rather than a controlling, micro-management style, are more likely to encourage greater workplace wellbeing and flourishing employees, according to the meta-analysis published in Springer’s Motivation and Emotion journal.

And the results are the same across all parts of the globe.

The research shows workers are more likely to be intrinsically motivated – or self-driven – when they can freely choose to pursue their work activities, feel they can master their tasks and are surrounded by important and supportive people like managers, mentors, peers and friends, finding a sense of relatedness.

“We found better workplace wellbeing and motivation when employees were not reliant on external events like rewards or sanctions,” said Melbourne Graduate School of Education study author Gavin Slemp.

“Our study showed that autonomy support leads to positive outcomes like , wellness, engagement and more committed and loyal employees, no matter the national culture,” Dr. Slemp said.

“We explored these leadership behaviours in studies that had accumulated more than 30,000 employees from all over the world and results were similar no matter the location.”

The research shows people who are intrinsically motivated do not need external rewards because the activity itself, that is self-driven, is its own .

“These practices have a positive influence on  work , performance and psychological functioning. Employees are less likely to suffer from burnout,” Dr. Slemp said.

“They might seek out new challenges and learning opportunities or take steps to develop relationships with peers. Decades of research document the positive effects of satisfying these three needs of autonomy, competence and relatedness—and autonomy support is an important contributor.”

The study shows an autonomy-supportive leader will: provide opportunities for staff to make their own choices and have input into decisions; encourage self-initiated behaviours within structured guidance and boundaries; and show interest in their perspective and demonstrate empathic concern while avoiding controls that restrain  or sanctions or rewards.

Breakthrough in Making Much Less Addictive Opioids

Important research this is, for it shows that the powerful pain relief opioids provide doesn’t have to be such a dangerous double-edged sword.

In the US, more than one-third of the population experiences some form of acute or chronic pain; in older adults this number rises to 40 percent.

The most common condition linked to chronic pain is chronic depression, which is a major cause of suicide.

To relieve severe pain, people go to their physician for powerful prescription painkillers, opioid drugs such as morphine, oxycodone and hydrocodone.

Almost all the currently marketed opioid drugs exert their analgesic effects through a protein called the “mu opioid receptor” (MOR).

MORs are embedded in the surface membrane of brain cells, or neurons, and block pain signals when activated by a drug.

However, many of the current opioids stimulate portions of the brain that lead to additional sensations of “rewarding” pleasure, or disrupt certain physiological activities. The former may lead to addiction, or the latter, death.

Which part of the brain is activated plays a vital role in controlling pain. For example, MORs are also present in the brain stem, a region that controls breathing.

Activating these mu receptors not only dulls pain but also slows breathing. Large doses stop breathing, causing death.

Activating MORs in other parts of the brain, including the ventral tegmental area and the nucleus accumbens, block pain and trigger pleasure or reward, which makes them addictive. But so far there is no efficient way to turn these receptors “on” and “off” in specific areas.

But there is another approach because not all opioids are created equal. Some, such as morphine, bind to the receptor and activate two signaling pathways: one mediating pain cessation and the other producing side effects like respiratory depression.

Other drugs favor one pathway more than the other, like only blocking pain – this is the one we want.

“Biased opioids” to kill pain

But MOR isn’t the only opioid receptor. There are two other closely related proteins called kappa and delta, or KOR and DOR respectively, that also alter pain perception but in slightly different ways.

Yet, currently there are only a few opioid medications that target KOR, and none that target DOR. One reason is that the function of these receptors in the brain neurons remains unclear.

Recently KOR has been getting attention as extensive studies from different academic labs show that it blocks pain without triggering euphoria, which means it isn’t addictive.

Another benefit is that it doesn’t slow respiration, which means that it isn’t lethal. But although it isn’t as dangerous as MOR, activating KOR does promote dysphoria, or unease, and sleepiness.

This work suggests it is possible to design a drug that only targets the pain pathway, without side effects. These kind of drugs are called “biased” opioids.

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The exciting news is that researchers in the Roth lab have discovered several promising compounds based on the KOR structure that selectively binds and activates KOR, without cavorting with the more than 330 other related protein receptors.

Now our challenge is to transform these molecules into safer drugs.

Health Benefits of ASMR Found in First Study of Its Kind

ASMR provides calming and stimulating sensation with no downsides currently known. It’s worth noting that the phenomenon hasn’t been researched much yet though — there may be more positives or negatives discovered in the future. There’s still an amazing amount that isn’t scientifically known about various aspects of the human mind.

Autonomous Sensory Meridian Response (ASMR) — the relaxing ‘brain tingles’ experienced by some people in response to specific triggers, such as whispering, tapping and slow hand movements — may have benefits for both mental and physical health, according to new research.

Almost 1000 New Genes Related to Intelligence Found

The deeper understanding of intelligence allows for it to be recreated, utilized and optimized more effectively. There are certainly more than enough problems in the world — more intelligence could be very helpful in solving them.

Researchers have identified over 1,016 specific genes associated with intelligence, the vast majority of which are unknown to science.

An international team conducted a large-scale genetic association study of intelligence and discovered 190 new genomic loci and 939 new genes linked with intelligence, significantly expanding our understanding of the genetic bases of cognitive function.

Led by statistical geneticist Danielle Posthuma from Vrije Universiteit Amsterdam in the Netherlands, the researchers performed a genome-wide association study (GWAS) of almost 270,000 people from 14 independent cohorts of European ancestry.

All these people took part in neurocognitive tests that measured their intelligence, and when researchers contrast their scores with variations in the participants’ DNA – called single nucleotide polymorphisms (SNPs) – you can see which mutations are associated with high intelligence.

From over 9 million mutations detected in the sample, Posthuma’s team identified 205 regions in DNA code linked with intelligence (only 15 of which had been isolated before), and 1,016 specific genes (77 of which had already been discovered).

According to the team, the genes that make for smartness also look to confer a protective effect to overall cognitive health, with the analysis finding a negative correlation with Alzheimer’s disease, attention deficit/hyperactivity disorder, depressive symptoms, and schizophrenia.

The intelligence genes were however correlated with increased instances of autism, and also longevity, suggesting people with these genetic underpinnings of high intelligence are more likely to live longer.

“Our results indicate overlap in the genetic processes involved in both cognitive functioning and neurological and psychiatric traits and provide suggestive evidence of causal associations that may drive these correlations,” the researchers write.

“These results are important for understanding the biological underpinnings of cognitive functioning and contribute to understanding of related neurological and psychiatric disorders.”