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Aging, Autoimmune Disease, Immunology, Infectious Disease, Research, Stanford News

Our aging immune systems are still in business, but increasingly thrown out of balance

Our aging immune systems are still in business, but increasingly thrown out of balance

business as usual

Stanford immunologist Jorg Goronzy, MD, told me a few years ago that a person’s immune response declines slowly but surely starting at around age 40. “While 90 percent of young adults respond to most vaccines, after age 60 that response rate is down to around 40-45 percent,” he said. “With some vaccines, it’s as low as 20 percent.”

A shaky vaccine response isn’t the only immune-system slip-up. With advancing age, we grow increasingly vulnerable to infection (whether or not we’ve been vaccinated), autoimmune disease (an immune attack on our own tissues) and cancer (when a once well-behaved cell metamorphoses into a ceaselessly dividing one).

A new study led by Goronzy and published in Proceedings of the National Academy of Sciences, suggests why that may come about. The culprit he and his colleagues have fingered turns out not to be the most likely suspect: the thymus.

This all-important organ’s job is to nurture an army of specialized  immune cells called T cells. (The “T” is for “Thymus.”) T cells are capable of recognizing and mounting an immune response to an unbelievably large number of different molecular shapes, including ones found only on invading pathogens or on our own cells when they morph into incipient tumor cells.

Exactly which feature a given T cell recognizes depends on the structure of a receptor molecule carried in abundance on that T cell’s surface.  Although each T cell sports just one receptor type, in the aggregate the number of different shapes T-cells recognize is gigantic, due to a high rate of reshuffling and mutation in the genes dictating their receptors’ makeup. (Stanford immunologist Mark Davis, PhD, perhaps more than any other single individual,  figured out in the early 1980s how this all works.)

T cells don’t live forever, and their generation from scratch completely depends on the thymus. Yet by our early teens the organ,  situated  in front of the lungs at the midpoint of our chest, starts shriveling up and replaced by (sigh – you knew this was coming)  fat tissue.

After the thymus melts away,  new T-cells come into being only when already-existing ones undergo cell division, for example to compensate for the attrition of their neighbors in one or another immune-system dormitory (such as bone marrow, spleen or a lymph node).

It’s been thought that the immune-system’s capacity to recognize and mount a response to pathogens (or incipient tumors) fades away because with age-related T-cell loss comes a corresponding erosion of diversity:  We just run out of T-cells with the appropriate receptors.

The new study found otherwise.  “Our study shows that the diversity of the human T-cell receptor repertoire is much higher than previously assumed, somewhere in the range of one billion different receptor types,” Goronzy says. “Any age-associated loss in diversity is trivial.” But the study also showed an increasing imbalance, with some subgroups of T cells (characterized by genetically identical  receptors)  hogging the show and other subgroups becoming vanishingly scarce.

The good news is that the players in an immune response are all still there, even in old age. How to restore that lost balance is the question.

Previously: How to amp up an aging immune response, Age-related drop in immune responsiveness may be reversible and Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before
Photo by Lars Plougmann

Autoimmune Disease, Evolution, Immunology, Microbiology, Nutrition, Public Health, Stanford News

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

hunter-gatherer cafe

Our genes have evolved a bit over the last 50,000 years of human evolution, but our diets have evolved a lot. That’s because civilization has transitioned from a hunter-gatherer lifestyle to an agrarian and, more recently and incompletely, to an industrialized one. These days, many of us are living in an information-intensive, symbol-analyzing, button-pushing, fast-food-munching society. This transformation has been accompanied by consequential twists and turns regarding what we eat, and how and when we eat it.

Toss in antibiotics, sedentary lifestyles, and massive improvements in public sanitation and personal hygiene, and now you’re talking about serious shake-ups in how many and which microbes we get exposed to – and how many of which ones wind up inhabiting our gut.

In a review published in Cell Metabolism, Stanford married-microbiologist couple Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, warn that modern civilization and its dietary contents may be putting our microbial gut communities, and our health, at risk.

[S]tudies in recent years have implicated [dysfunctional gut-bug communities] in a growing list of Western diseases, such as metabolic syndrome, inflammatory bowel disease, and cancer. … The major dietary shifts occurring between the hunter-gatherer lifestyle, early Neolithic farming, and more recently during the Industrial Revolution are reflected in changes in microbial membership within dental tartar of European skeletons throughout these periods. … Traditional societies typically have much lower rates of Western diseases.

Every healthy human harbors an interactive internal ecosystem consisting of something like 1,000 species of intestinal microbes.  As individuals, these resident Lilliputians may be tiny, but what they lack in size they make up in number. Down in the lower part of your large intestine dwell tens of trillions of  single-celled creatures – a good 10 of them for every one of yours. If you could put them all on a scale, they would cumulatively weigh about four pounds. (Your brain weighs three.)

Together they do great things. In a Stanford Medicine article I wrote a few years back, “Caution: Do Not Debug,” I wrote:

The communities of micro-organisms lining or swimming around in our body cavities … work hard for their living. They synthesize biomolecules that manipulate us in ways that are helpful to both them and us. They produce vitamins, repel pathogens, trigger key aspects of our physiological development, educate our immune system, help us digest our food and for the most part get along so well with us and with one other that we forget they’re there.

But when our internal microbes don’t get enough of the right complex carbohydrates (ones we can’t digest and so pass along to our neighbors downstairs), they may be forced to subsist on the fleece of long carbohydrate chains (some call it “mucus”)  lining and guarding the intestinal wall. Weakening that barrier could encourage inflammation.

The Sonnenburgs note that certain types of fatty substances are overwhelmingly the product of carbohydrate fermentation by gut microbes. These substances have been shown to exert numerous anti-inflammatory effects in the body, possibly protecting against asthma and eczema: two allergic conditions whose incidence has soared in developed countries and seems oddly correlated with the degree to which the environment a child grows up in is spotlessly hygienic.

Previously: Joyride: Brief post-antibiotic sugar spike gives pathogens a lift, The future of probiotics and Researchers manipulate microbes in the gut
Photo by geraldbrazell

Bioengineering, Cardiovascular Medicine, Neuroscience, Research, Stanford News, Stroke

Targeted stimulation of specific brain cells boosts stroke recovery in mice

big blue brainThere are 525,949 minutes in a year. And every year, there are about 800,000 strokes in the United States – so, one stroke every 40 seconds. Aside from the infusion, within three or four hours of the stroke, of a costly biological substance called tissue plasminogen activator (whose benefit is less-than-perfectly established), no drugs have been shown to be effective in treating America’s largest single cause of neurologic disability and the world’s second-leading cause of death. (Even the workhorse post-stroke treatment, physical therapy, is far from a panacea.)

But a new study, led by Stanford neurosurgery pioneer Gary Steinberg and published in Proceedings of the National Academy of Sciences, may presage a better way to boost stroke recovery. In the study, Steinberg and his colleagues used a cutting-edge technology to directly stimulate movement-associated areas of the brains of mice that had suffered strokes.

Known as optogenetics – whose champion, Stanford psychiatrist and bioengineer Karl Deisseroth, co-authored the study – the light-driven method lets investigators pinpoint a specific set of nerve cells and stimulate only those cells. In contrast, the electrode-based brain stimulation devices now increasingly used for relieving symptoms of Parkinson’s disease, epilepsy and chronic pain also stimulate the cells’ near neighbors.

“We wanted to find out whether activating these nerve cells alone can contribute to recovery,” Steinberg told me.

As I wrote in a news release  about the study:

By several behavioral … and biochemical measures, the answer two weeks later was a strong yes. On one test of motor coordination, balance and muscular strength, the mice had to walk the length of a horizontal beam rotating on its axis, like a rotisserie spit. Stroke-impaired mice [in which the relevant brain region] was optogenetically stimulated did significantly better in how far they could walk along the beam without falling off and in the speed of their transit, compared with their unstimulated counterparts. The same treatment, applied to mice that had not suffered a stroke but whose brains had been … stimulated just as stroke-affected mice’s brains were, had no effect on either the distance they travelled along the rotating beam before falling off or how fast they walked. This suggests it was stimulation-induced repair of stroke damage, not the stimulation itself, yielding the improved motor ability.

Moreover, levels of some important natural substances called growth factors increased in a number of brain areas in  optogenetically stimulated but not unstimulated post-stroke mice. These factors are key to a number of nerve-cell repair processes. Interestingly, some of the increases occurred not only where stimulation took place but in equivalent areas on the opposite side of the brain, consistent with the idea that when we lose function on one side of the brain, the unaffected hemisphere can step in to help restore some of that lost function.

Translating these findings into human trials will mean not just brain surgery, but also gene therapy in order to introduce a critical light-sensitive protein into the targeted brain cells. Steinberg notes, though, that trials of gene therapy for other neurological disorders have already been conducted.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, BE FAST: Learn to recognize the signs of stroke and Light-switch seizure control? In a bright new study, researchers show how
Photo by Shutterstock.com

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Aging, Genetics, Imaging, Immunology, Mental Health, Neuroscience, Research, Women's Health

Stanford’s brightest lights reveal new insights into early underpinnings of Alzheimer’s

Stanford's brightest lights reveal new insights into early underpinnings of Alzheimer's

manAlzheimer’s disease, whose course ends inexorably in the destruction of memory and reason, is in many respects America’s most debilitating disease.  As I wrote in my article, “Rethinking Alzheimer’s,” just published in our flagship magazine Stanford Medicine:

Barring substantial progress in curing or preventing it, Alzheimer’s will affect 16 million U.S. residents by 2050, according to the Alzheimer’s Association. The group also reports that the disease is now the nation’s most expensive, costing over $200 billion a year. Recent analyses suggest it may be as great a killer as cancer or heart disease.

Alarming as this may be, it isn’t the only news about Alzheimer’s. Some of the news is good.

Serendipity and solid science are prying open the door to a new outlook on what is arguably the primary scourge of old age in the developed world. Researchers have been taking a new tack – actually, more like six or seven new tacks – resulting in surprising discoveries and potentially leading to novel diagnostic and therapeutic approaches.

As my article noted, several Stanford investigators have taken significant steps toward unraveling the tangle of molecular and biochemical threads that underpin Alzheimer’s disease. The challenge: weaving those diverse strands into the coherent fabric we call understanding.

In a sidebar, “Sex and the Single Gene,” I described some new work showing differential effects of a well-known Alzheimer’s-predisposing gene on men versus women – and findings about the possibly divergent impacts of different estrogen-replacement  formulations on the likelihood of contracting dementia.

Coming at it from so many angles, and at such high power, is bound to score a direct hit on this menace eventually. Until then, the word is to stay active, sleep enough and see a lot of your friends.

Previously: The reefer connection: Brain’s “internal marijuana” signaling implicated in very earliest stages of Alzheimer’s pathology, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Protein known for initiating immune response may set up our brains for neurodegenerative disease, Estradiol – but not Premain – prevents neurodegeneration in woman at heightened dementia risk and Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women, but not for men
Illustration by Gérard DuBois

Behavioral Science, Chronic Disease, Neuroscience, Pain, Research, Stanford News

Obscure brain chemical indicted in chronic-pain-induced “Why bother?” syndrome

Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

why botherChronic pain, meaning pain that persists for months and months or even longer (sometimes continuing well past the time when the pain-causing injury has healed), is among the most abundant of all medical afflictions in the developed world. Estimates of the number of people with this condition in the United States alone range from 70 million to 116 million adults – in other words, as much as half the country’s adult population!

No picnic in and of itself, chronic pain piles insult on injury. It differs from a short-term episode of pain not only in its duration, but also in triggering in sufferers a kind of psychic exhaustion best described by the rhetorical question, “Why bother?”

In a new study in Science, a team led by Stanford neuroscientist Rob Malenka, MD, PhD, has identified a particular nerve-cell circuit in the brain that may explain this loss of motivation that chronic pain all too often induces. Using lab mice as test subjects, they showed that mice enduring unremitting pain lost their willingness to perform work in pursuit of normally desirable goals, just as people in chronic pain frequently do.

It wasn’t that these animals weren’t perfectly capable of carrying out the tasks they’d been trained to do, the researchers showed. Nor was it that they lost their taste for the food pellets which with they were rewarded for successful performance – if you just gave them the food, they ate every bit as much as normal mice did. But they just weren’t willing to work very hard to get it. Their murine morale was shot.

Chalk it up to the action of a mysterious substance used in the brain for god-knows-what. In our release describing the study, I explained:

Galanin is a short signaling-protein snippet secreted by certain cells in various places in the brain. While its presence in the brain has been known for a good 60 years or so, galanin’s role is not well-defined and probably differs widely in different brain structures. There have been hints, though, that galanin activity might play a role in pain. For example, it’s been previously shown in animal models that galanin levels in the brain increase with the persistence of pain.

In a surprising and promising development, the team also found that when they blocked galanin’s action in a particular brain circuit, the mice, while still in as much pain as before, were once again willing to work hard for their supper.

Surprising, because galanin is a mighty obscure brain chemical, and because its role in destroying motivation turns out to be so intimate and specific. Promising, because the discovery suggests that a drug that can inhibit galanin’s activity in just the implicated brain circuit, without messing up whatever this mystery molecule’s more upbeat functions in the brain might be, could someday succeed in bringing back that drive to accomplish things that people in chronic pain all too often lose.

Previously: “Love hormone” may mediate wider range of relationships than previously thought, Revealed: the brain’s molecular mechanism behind why we get the blues, Better than the real thing: How drugs hot-wire our brain’s reward circuitry and Stanford researchers address the complexity of chronic pain
Photo by Doug Waldron

Behavioral Science, Bioengineering, Neuroscience, Research, Stanford News, Technology

Party animal: Scientists nail “social circuit” in rodent brain (and probably ours, too)

Party animal: Scientists nail "social circuit" in rodent brain (and probably ours, too)

party animalStimulating a single nerve-cell circuit among millions in the brain instantly increases a mouse’s appetite for getting to know a strange mouse, while inhibiting it shuts down the same mouse’s drive to socialize with the stranger.

Stanford brain scientist and technology whiz Karl Deisseroth, MD, PhD, is already renowned for his role in developing optogenetics, a technology that allows researchers to turn on and turn off nerve-cell activity deep within the brain of a living, freely roving animal so they can see the effects of that switching in real time. He also pioneered CLARITY, a method of rendering the brain – at least if it’s the size of of a mouse’s – both transparent and porous so its anatomy can be charted, even down to the molecular level, in ways previously deemed unimaginable.

Now, in another feat of methodological derring-do detailed in a new study in Cell, Deisseroth and his teammates incorporated a suite of advanced lab technologies, including optogenetics as well as a couple of new tricks, to pinpoint a particular assembly of nerve cells projecting from one part to another part of the mouse brain. We humans’ brains obviously differ in some ways from those of mice. But our brains have the same connections Deisseroth’s group implicated in mice’s tendency to seek or avoid social contact. So it’s a good bet this applies to us, too.

Yes, we’d all like to be able to flip a switch and turn on our own “party animal” social circuitry from time to time. But the potential long-term applications of advances like this one are far from frivolous. The new findings may throw light on psychiatric disorders marked by impaired social interaction such as autism, social anxiety, schizophrenia and depression.From my release on this study:

“Every behavior presumably arises from a pattern of activity in the brain, and every behavioral malfunction arises from malfunctioning circuitry,” said Deisseroth, who is also co-director of Stanford’s Cracking the Neural Code Program. “The ability, for the first time, to pinpoint a particular nerve-cell projection involved in the social behavior of a living, moving animal will greatly enhance our ability to understand how social behavior operates, and how it can go wrong.”

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Researchers induce social deficits associated with autism, schizophrenia in mice, Anti-anxiety circuit found in unlikelybrain region and Using light to get muscles moving
Photo by Gamerscore blog

Neuroscience, Research, Stanford News

The reefer connection: Brain’s “internal marijuana” signaling system implicated in very early stages of Alzheimer’s pathology

The reefer connection: Brain's "internal marijuana" signaling system implicated in very early stages of Alzheimer's pathology

funny brain cactusIt’s axiomatic that every psychoactive drug works by mimicking some naturally occurring, evolutionarily adaptive, brain-produced substance. Cocaine and amphetamines mimic some aspects of a signaling chemical in the brain called dopamine. Heroine, morphine, and codeine all mimic neuropeptides called endorphins.

Tetrahydrocannabinol, the active component in mariuana and hashish, is likewise a doppleganger for a set of molecules in the brain called endocannabinoids. The latter evolved not to get us high but to perform numerous important signaling functions known and unknown. One of those is, as Stanford neuroscientist Dan Madison, PhD, puts it, to “open up the learning gate.”

In a key mammalian brain structure called the hippocampus,  which serves as (among other things) a combination GPS system and memory-filing assistant, endocannabinoids act as signal boosters for a key nerve tract – akin to transformers spaced along a high-voltage electrical transmission cable.

But the endocannabinoid system is highly selective in regard to which signals it boosts. Its overall effect in the hippocampus is to separate the wheat from the chaff (or in this case, would it be appropriate to say “the leaves from the seeds and stems”?). This ensures that real information (e.g., “that looks like some food!” or “I remember being here before”) gets passed down the line to the next relay station in the brain’s information-processing assembly line.

A new study in Neuron by Madison and his colleagues shows a likely link between the brain’s endocannabinoid system and a substance long suspected of playing a major, if mysterious, role in initiating Alzheimer’s disease. As I wrote in a release accompanying the study’s publication:

A-beta — strongly suspected to play a key role in Alzheimer’s because it’s the chief constituent of the hallmark clumps dotting the brains of people with Alzheimer’s — may, in the disease’s earliest stages, impair learning and memory by blocking the natural, beneficial action of endocannabinoids in the brain.

This interference with the “learning gate” occurs when A-beta is traveling in tiny, soluble clusters of just a few molecules, long before it aggregates into those textbook clumps. So does it follow that we should all start smoking pot to prevent Alzheimer’s disease?

Hardly. Again, from my release:

Madison said it would be wildly off the mark to assume that, just because A-beta interferes with a valuable neurophysiological process mediated by endocannabinoids, smoking pot would be a great way to counter or prevent A-beta’s nefarious effects on memory and learning ability… “Endocannabinoids in the brain are very transient and act only when important inputs come in,” said Madison … “Exposure to marijuana over minutes or hours is different: more like enhancing everything indiscriminately, so you lose the filtering effect. It’s like listening to five radio stations at once.”

It may even be that A-beta (ubiquitously produced by all the body’s cells), in the right amounts at the right times, is itself performing a crucial if still obscure service: fine-tuning a process that fine-tunes another process that tweaks the circuitry of learning and remembering.

Previously: The brain makes its own Valium: Built-in seizure brake?, How villainous substance starts wrecking synapses long before clumping into Alzheimer’s plaques and Black hat in Alzheimer’s, white hat in multiple sclerosis?
Photo by Phing

Health Policy, Infectious Disease, Microbiology, Public Health, Stanford News

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Dr. Milana Trounce, M.D. teaches a class on the the risks of bioterror at the Stanford School of Medicine. Photo taken on Monday, April 21, 2014. ( Norbert von der Groeben/ Stanford School of Medicine )

“What if nuclear bombs could reproduce? Get your hands on one today, and in a week’s time you’ve got a few dozen.”

That’s the lead sentence of a feature article I just wrote for Inside Stanford Medicine. The answer is, bombs can’t reproduce. But something just as potentially deadly – and a whole lot easier to come by – can, and does.

What I learned in the course of writing the feature, titled “How contagious pathogens could lead to nuke-level casualties” (I encourage you to take a whack at it), was bracing. Stanford surgeon Milana Trounce, MD, who specializes in emergency medicine, has been teaching a course that pulls together students, faculty and outside experts from government, industry and academia. Her goal is to raise awareness and inspire collaborations on the thorny multidisciplinary problems posed by the very real prospect that somebody, somewhere, could very easily be producing enough killer germs to wipe out huge numbers of people – numbers every bit as large as those we’ve come to fear in the event of a nuclear attack.

Among those I quote in the article are infectious-disease expert David Relman, MD, and biologist/applied physicist Steven Block, PhD, both of whom have sat in on enough closed-door meetings to know that bioterrorism is something we need to take seriously.

Not only do nukes not reproduce. They don’t leap from stranger to stranger, or lurk motionless in midair or on fingertips. Nor can they be fished from soil and streams or cheaply conjured up in a clandestine lab in someone’s basement or backyard.  One teaspoon of the toxin produced by the naturally occurring bacterial pathogen Clostridium botulinum is enough to kill several hundreds of thousands of people. That’s particularly scary when you consider that this toxin – better known by the nickname “Botox” -  is already produced commercially for sale to physicians who inject it into their patients’ eyebrows.

As retired Rear Adm. Ken Bernard, MD, a former special assistant on biosecurity matters to Presidents Bill Clinton and George W. Bush and a guest speaker for Trounce’s Stanford course, put it: “Who can be sure there’s no off-site, illegal production? Suppose a stranger were to say, ‘I want 5 grams — here’s $500,000’?

That’s five grams, as in one teaspoon. As I just mentioned, we’re talking hundreds of thousands of people killed, if this spoonful were to, say, find its way into just the right point in the milk supply chain (the point where loads of milk from numerous scattered farms get stored in huge holding tanks before being parsed out to myriad delivery trucks). That’s pretty stiff competition for a hydrogen bomb. For striking terror into our hearts, the only thing bioweapons lack is branding – nothing tops that mushroom-cloud logo.

Previously: Stanford bioterrorism experts comments on new review of anthrax case and Show explores scientific questions surrounding 2001 anthrax attacks
Photo of Milana Trounce by Norbert von der Groeben

Fertility, Health and Fitness, Men's Health, Public Health, Research, Stanford News

Poor semen quality linked to heightened mortality rate in men

Poor semen quality linked to heightened mortality rate in men

sperm graffitiMen with multiple defects in their semen appear to be at increased risk of dying sooner than men with normal semen, according to a study of some  12,000 men who were evaluated at two different centers specializing in male-infertility problems.

In that study, led by Michael Eisenberg, MD, PhD, Stanford’s director of male reproductive medicine and surgery, men with more than one such defect such as reduced total semen volume, low sperm counts or motility, or aberrant sperm shape were more than twice as likely to die, over a seven-and-a-half-year follow-up period, than men found to be free of such issues.

Given that one in seven couples in developed countries encounter fertility problems at some point, Eisenberg told me, a two-fold increase in mortality rates qualifies as a serious health issue. As he told me for an explanatory release I wrote about the study:

“Smoking and diabetes — either of which doubles mortality risk — both get a lot of attention… But here we’re seeing the same doubled risk with male infertility, which is relatively understudied.”

Moreover, the difference was statistically significant, despite the fact that relatively few men died, due primarily to their relative youth (typically between 30 and 40 years old) when first evaluated. And the difference persisted despite the researchers’ efforts to control for differences in health status and age between the two groups.

Eisenberg has previously found that childless men are at heightened risk of death from cardiovascular disease and that men with low sperm production face increased cancer risk.

Previously:  Men with kids are at lower risk of dying from cardiovascular disease than their childless counterparts and Low sperm count can mean increased cancer risk
Photo by Grace Hebert

Aging, Mental Health, Neuroscience, Research, Stanford News, Stem Cells

The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning

The rechargeable brain: Blood plasma from young mice improves old mice's memory and learning

brain battery“Maybe Ponce de Leon should have considered becoming a vampire,” I noted here a few years ago. In a related Stanford Medicine article, I elaborated on that point (i.e. Dracula may have been on to something):

Count Dracula may have been bloodthirsty, but nobody ever called him stupid. If that practitioner of what you could call “the Transylvanian transfusion” knew then what we know now, it’s a good bet he was keeping his wits as sharp as his teeth by restricting his treats to victims under the age of 30.

I was referring then to an amazing discovery by Stanford brain-degeneration expert Tony Wyss-Coray, PhD, and his then-graduate student Saul Villeda, PhD, who now has his own lab at the University of California-San Francisco. They’d found that something in an old mouse’s blood could somehow exert an aging effect on the capabilities of a young mouse’s brain, and you know that ain’t good. They’d even pinpointed one specific substance (eotaxin) behind this effect, implying that inhibiting this naturally produced and sometimes very useful chemical’s nefarious action – or, if you’re a vampire, laying off the old juice and  getting your kicks from preteens when available – might be beneficial to aging brains.

But I was premature. While the dynamic duo had shown that old blood is bad for young brains and had also demonstrated that old mice’s brains produce more new nerve cells (presumably a good thing) once they’ve had continuous exposure to young mice’s blood, the researchers hadn’t yet definitively proven that the latter translated into improved intellectual performance.

This time out they’ve gone and done just that, in a study (subscription required) published online yesterday in Nature Medicine. First they conducted tricky, sophisticated experiments to show that when the old mice were continuously getting blood from young mice, an all-important region in a mouse’s brain (and yours) called the hippocampus perks up biochemically, anatomically and physiologically: It looks and acts more like a younger mouse’s hippocampus. That’s big, because the hippocampus is not only absolutely essential to the formation of new memories but also the first brain region to go when the early stirrings of impending dementia such as Alzheimer’s start subtly eroding brain function, long before outwardly observable symptoms appear.

Critically, when Wyss-Coray, Villeda and their comrades then administered a mousey IQ test (a standard battery of experiments measuring mice’s ability to learn and remember) to old mice who’d been injected with plasma (the cell-free part of blood) from healthy young mice, the little codgers far outperformed their peers who got crummy old-mouse plasma instead.

Slam dunk.

“This could have been done 20 years ago,” Wyss-Coray told me when I was assembling my release on this study. “You don’t need to know anything about how the brain works. You just give an old mouse young blood and see if the animal is smarter than before. It’s just that nobody did it.”

Previously: When brain’s trash collectors fall down on the job, neurodegeneration risk picks up, Brain police: Stem cells’ fecund daughters also boss other cells around, Old blood + young brain = old brain and Might immune response to viral infections slow birth of new nerve cells in brain?
Photo by Takashi Hososhima

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