Copy-and-paste

I'm really interested in research on aging, and I'd like to think that it's not solely because I'm Of A Certain Age myself.  The whole fact of our undergoing age-related system degradation is fascinating -- more so when you realize that other vertebrates age at dramatically different rates.  Mice and rats age out after about a year and a half to two years; dogs (sadly) rarely make it past fifteen (much less in some breeds); and the Galapagos Tortoise can still be hale and hearty at two hundred years of age.

A lot of research has gone into why different organisms age at such different speeds, and (more importantly) how to control it.  The ultimate goal, selfish though it may sound, is extending the healthy human life span.  Imagine if we reached our healthy adult physiology at (say) age twenty-five or so, and then went into stasis with respect to aging for two hundred or three hundred years -- or more?

Heady stuff.  For me, the attraction is not so much avoiding death (although that's nice, too).  I was just chatting with a friend yesterday about the fact that one of my biggest fears is being dependent on others for my care.  The idea of my body and/or mind degrading to the point that I can no longer care for my own needs is profoundly terrifying to me.  And when you add to the normal age-related degradation the specter of diseases such as Alzheimer's and ALS -- well, all I can say is that I agree with my dad, who said that compared with that fate, "I'd rather get run over by a truck."

Leaving that aside, though, a particularly interesting piece of research that has bearing on this field was published last week in the journal Science Advances.  But to understand it, you have to know a little bit about a peculiarity of genetics first.

Several decades ago, a geneticist named Barbara McClintock was working with patterns of seed color inheritance in "Indian corn."  In this variety, one cob can bear seeds with dozens of different colors and patterns.  After much study, she concluded that her data could only be explained by there being "transposable elements" -- genetic sequences that were either clipped out and moved, or else copied and moved -- functions similar to the "cut-and-paste" and "copy-and-paste" commands on your computer. McClintock wrote a paper about it...

... and was immediately ignored.  For one thing, she was a woman in science, and back when she was doing her research -- in the 1960s and 1970s -- that was sufficient reason to discount it.  Her colleagues derisively nicknamed her theory "jumping genes" and laughed it into oblivion.

Except that McClintock wouldn't let it go.  She was convinced she was right, and kept doggedly pursuing more data, data that would render her conclusion incontrovertible.  She found it -- and won the Nobel Prize in Physiology and Medicine in 1983, at the age of 81.

Barbara McClintock in her laboratory at Cold Spring Harbor [Image licensed under the Creative Commons Smithsonian Institution/Science Service; Restored by Adam Cuerden, Barbara McClintock (1902-1992) shown in her laboratory in 1947]

McClintock's "transposable elements" (now called "transposons") have since been found in every vertebrate studied.  They are used to provide additional copies of essential genes, so that if one copy succumbs to a mutation, there's an extra working copy that can take over.  They're also used in gene switching.  Move a gene near an on-switch called a promoter, and it turns on; move it away, and it turns off.

The problem is, like any natural process, it can go awry.  The copy-and-paste function especially seems to have that tendency.  When it malfunctions, it acts like a runaway copy-and-paste would in your word processing software.  Imagine the havoc that would ensue if you had an important document, and the computer went haywire and inserted one phrase over and over again in random points in the text.

This should give you an idea of why it's so important to keep this process under control.

You have a way of taking care of these "rogue transposons" (as they're called).  One such mechanism is methylation, which is a chemical means of tangling up and permanently shutting down genes.  But the paper just released suggests that aging is (at least in part) due to the rogue transposition of one particular sequence getting ahead of methylation, leaving a particular chunk of DNA scattered again and again across the genome.

The current research, out of New York University, looked at a transposon called Long Interspersed Nuclear Element 1 (LINE-1) that has become especially good at this copy-and-paste trick, to the extent that the human genome contains five hundred thousand copies of it -- a full twenty percent of our genetic material.  The researchers found that LINE-1 can only accomplish this self-insertion when a molecule called ORF1p is present in sufficient quantities to assemble into clumps called condensates.  Find a way to block ORF1p, and LINE-1 is effectively disabled -- potentially slowing down age-related genetic malfunction.

Of course, even in the best-case scenario, it's unlikely that tweaking one molecule will affect overall aging in any kind of dramatic way.  Even so, the whole thing is tremendously interesting.  On the other hand, I have to say that the idea that we are getting to the point that we can tinker around with fundamental processes like aging is a little frightening.  It opens up practical and ethical issues we've never had to consider before.  How this would affect human population growth?  Who would have access to such genetic modifications if they proved effective and safe?  You can bet the rich would have first dibs (and the last thing we need is Rupert Murdoch living to two hundred years old.)  

Even such things as how we approach the idea of careers and retirement would require significant rethinking.  Imagine if you reached the age of sixty and could expect another fifty or more years of active health.  More staggering still is if the effect on humans was greater -- and the upper bound of human life span was increased to two hundred or three hundred years.  It seems like science fiction, but with the research that is currently happening, it's not outside of the realm of possibility.

Who would want to retire at sixty if you still had the physiology and mental acuity of a twenty-five year old?  At the same point, who would want to stay in the same job for another hundred years or more? 

The whole thing would require a drastic reorganization of our society, a far more pervasive set of changes than any scientific discovery has yet caused.  And lest you think that I'm exaggerating the likelihood of such an eventuality; remember how much progress has happened in biological science in the last century.  Only a hundred years ago, children in industrialized countries were still dying by the thousands of diphtheria and measles.  There were dozens of structures in cells, and a good many organs in humans, about whose function we knew essentially nothing.  We knew that DNA existed, but had no idea that it was the genetic material, much less how it worked.

Makes you wonder what our understanding will be in another hundred years, doesn't it?

And maybe some of the people reading this right now will be around to see it.

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Gold standard

I have a great fondness for a glass of fine red wine or single malt scotch, but I have to admit something up front; to say I have an "undiscerning palate" is a considerable understatement.

I basically have two taste buds: "thumbs up" and "thumbs down."  I know what I like, but that's about where it stops.  On the other end of the spectrum from me are "supertasters" -- people who have a much greater acuity for the sense of taste than the rest of us slobs -- and they are in high demand working for food and drink manufacturers as taste testers, because they can pick up subtleties in flavor that bypass most people.  They're the ones we have to thank for what you read on the labels in wine stores ("This vintage has a subtle nose of asphalt and boiled cabbage; the flavor contains notes of wet dog, garlic, and sour cream, with a delicate hint of chocolate at the finish").

I make fun, but I swear I once saw a sauvignon blanc described as tasting like "cat piss on a gooseberry bush."  I had to try it.  

It was actually rather nice.  "Thumbs up."

What's always struck me about all this is how subjective it seems.  So much of it is, both literally and figuratively, a matter of taste.  This is why I thought it was fascinating that a new study has found a way to quantify the presence of congeners -- the chemicals other than alcohol introduced by the fermentation and aging processes -- which are the source of most of the flavor in wines, beers, and spirits.

[Image licensed under the Creative Commons Pjt56, Glencairn Glass-pjt, CC BY-SA 4.0]

A paper in ACS Applied Nanomaterials, led by Jennifer Gracie of the University of Glasgow, describes a simple test for flavor in whisky using less than a penny's worth of soluble gold ions.  It turns out that the aging process for whiskies involves storing them in charred oak barrels, and this introduces congeners that react strongly with gold, producing a striking red or purple color.  The deeper the color, the more congeners are present -- and the more flavorful the whisky.

The authors write:

The maturation of spirit in wooden casks is key to the production of whisky, a hugely popular and valuable product, with the transfer and reaction of molecules from the wooden cask with the alcoholic spirit imparting color and flavor.  However, time in the cask adds significant cost to the final product, requiring expensive barrels and decades of careful storage.  Thus, many producers are concerned with what “age” means in terms of the chemistry and flavor profiles of whisky.  We demonstrate here a colorimetric test for spirit “agedness” based on the formation of gold nanoparticles (NPs) by whisky.  Gold salts were reduced by barrel-aged spirit and produce colored gold NPs with distinct optical properties...  We conclude that age is not just a number, that the chemical fingerprint of key flavor compounds is a useful marker for determining whisky “age”, and that our simple reduction assay could assist in defining the aged character of a whisky and become a useful future tool on the warehouse floor.

Which is pretty cool.  Better than relying on people like me, whose approach to drinking a nice glass of scotch is not to analyze it, but to pour a second round.  I guess there's nothing wrong with knowing what you like -- even if you can't really put your finger on why you like it.

That's why we non-supertasters rely on studies like this one to provide a gold standard to make up for our own lack of perceptivity.

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Golden years gold medal

You've probably heard the old joke about a man going in for major surgery.  "Doc," he says, right before the anesthetic is administered, "I gotta ask... after this surgery, will I be able to play the piano?"

The surgeon smiles reassuringly and says, "Of course you will."

"Awesome!" the man says.  "I've always wanted to play the piano!"

That's what came to mind when I read an article in Science called, "Will You Keep Winning Races Into Old Age?  Your Cells Hold Clues," by Tess Joosse.  I'm hoping that like the aspiring pianist, old age will put me into the winner's bracket, because since I started running semi-competitively forty years ago, I've yet to win a race.  I train, I run regularly, but I'm still (and probably always will be) a solid middle-of-the-packer.  The closest I've ever come was about three years ago, when I came in third in my age group.

To be scrupulously honest, there were only six people in my age group.  But I'll take my little victories wherever I can get them.

Me last year, about to not cross the finish line first

Be that as it may, I'm still in there trying.  I'm 61, and I know that regular exercise is essential not only for continuing physical health but mental wellbeing.  In fact, on June 8 I'm running in the Ithaca Twilight 5K, a wonderful race down the footpaths along Cayuga Lake, and because I'm recovering from a series of health setbacks I've lowered my sights to simply getting across the finish line without having to be carted over it in a wheelbarrow.

Even though the "will you keep winning?" part of the headline of the article struck me as funny, the research itself is pretty cool.  Russell Hepple, a biologist at the University of Florida, wondered what was going on with people who are still competitive racers even into old age -- such as his father-in-law, who holds the record time for an eighty-year-old in the Boston Marathon.  Hepple and his colleagues did an assay on the muscle tissue of world-class senior athletes and a group of non-athletes, and found no fewer than eight hundred proteins that were produced in amounts that were significantly different between the two groups.  Some were higher in the athletes; others were lower.  But one obvious patterns was that over half of the proteins the study found were ones that are expressed by, or otherwise affect, the mitochondria.

For some reason, the factoid "the mitochondria are the powerhouses of the cell" is one that sticks in the minds of just about everyone who has taken high school biology, but the way they work is actually pretty amazing.  Your mitochondria are actually symbiotic single-celled life-forms living inside your cells -- they even have their own DNA -- and they have evolved a complex series of chemical reactions (collectively known as aerobic cellular respiration) to break down glucose and store its energy in a molecule called ATP, which is the direct driver of damn near every process living things do.  The amount of ATP created and the rate at which it's used are in an incredibly tight balance; it's estimated that you produce (and consume/recycle) your body weight in ATP every day, which amounts to ten million ATP molecules per second, per cell.

So it's no surprise that octogenarian racers have better mitochondrial function than the rest of us slobs.  In fact, the study found that 176 of the proteins studied were unique to elite senior athletes; how much of that is because of a lucky combination of genes, and how much is because their continuous training has triggered protein production that in non-athletes tapers off or stops entirely, isn't known.

Also an open question is whether administering one or more of these proteins would boost aerobic exercise capacity in older people who aren't athletes (but would like to be).  Luigi Ferrucci of the National Institute on Aging, who co-authored the study, has proposed trying this in mice and seeing if it does increase endurance and stamina, without any untoward side effects.

In any case, I suspect that no matter what I do, I'll never be a gold medalist.  That's okay with me.  I love running for running's sake, and the race community (at least around here) is super supportive of everyone regardless of their level.  (At a race I was in a while back, a twelve-year-old boy had posted himself just past the finish line, and was high-fiving each runner as they crossed.  When I stumbled my way across, he grinned at me and said, "Well done, Shirtless Tattoo Guy!"  That, to me, encapsulates the spirit of racing in my area.)

But I'll be interested to see where this research leads.  Anything I can do to stave off decline (physical or mental) as I get older is a good thing.  Until then, though, I'll keep running, and keep being okay with finishing in the middle of the pack.

**************************************

Remembrance of things past

Like many People Of A Certain Age, I'm finding that my memory isn't what it used to be.

I walk into a room, and then say, "Why did I come in here?"  I'll think, "I don't need a grocery list, I'm just going for a few things," and come back with half of them.  We just had our dogs in for their annual checkups and shots, and there were a few things for each of them we wanted to ask the vet about.  My wife and I dutifully sat down and made a list -- and both of us forgot to put something on the list that we'd talked about only the previous day.

It's shown up, too, in more academic pursuits.  For my birthday last year my wife got me an online course through Udemy in beginning Japanese, a language I've always wanted to learn.  My dad had been stationed in Japan in the 1950s, and he learned enough of the language to get by; I grew up around the Japanese art and music my dad brought back with him, and became a Japanophile for life.  So I was thrilled to have the opportunity to study the country's unique and beautiful language.  The course starts out with a brief pronunciation guide, then launches into the hiragana -- one of three scripts used in written Japanese.  Each of the 46 characters stands for either a phoneme or a syllable, and some of them look quite a bit alike, so it's a lot to remember.  I have flash cards I made for all 46, and there are some I consistently miss, every single time I go through them.

When I flip the card over, my response is always, "Damn!  Of course!  Now I remember it!"  I recognize the character immediately, and can often even remember the mnemonic the teacher suggested to use in recalling it.  I'm getting there -- of the 46, there are about ten that I still struggle with -- but I know that twenty years ago, I'd have them all down cold by now.

Kids playing a memory game [Image is in the Public Domain]

Understandably, there's a nasty little thought in the back of my mind about senility and dementia.  My mother's sister had Alzheimer's -- to my knowledge, the only person in my extended family to suffer from that horrific and debilitating disease -- and I watched her slow slide from a smart, funny woman who could wipe the floor with me at Scrabble, did crossword puzzles in ink, and read voraciously, to a hollow, unresponsive shell.  I can think of no more terrifying fate. 

A new piece of research in Trends in Cognitive Science has to some extent put my mind at ease.  In "Cluttered Memory Representations Shape Cognition in Old Age," psychologists Tarek Amer (of Columbia University), Jordana Wynn (of Harvard University), and Lynn Hasher (of the University of Toronto) found that the forgetfulness a lot of us experience as we age isn't a simple loss of information, it's a loss of access to information that's still there, triggered by the clutter of memories from the past.

The authors write:

Wisdom and knowledge, cognitive functions that surely depend on being able to access and use memory, grow into old age.  Yet, the literature on memory shows that intentional, episodic memory declines with age.  How are we to account for this paradox?  To do so, we need to understand three aspects of memory differences associated with aging, two of which have received extensive investigation: age differences in memory encoding and in retrieval.  A third aspect, differences in the contents of memory representations, has received relatively little empirical attention.  Here, we argue that this aspect is central to a full understanding of age differences in memory and memory-related cognitive functions.  We propose that, relative to younger adults, healthy older adults (typically between 60 and 85 years of age) process and store too much information, the result of reductions in cognitive control or inhibitory mechanisms.  When efficient, these mechanisms enable a focus on target or goal-relevant information to the exclusion (or suppression) of irrelevant information.  Due to poor control (or reduced efficiency), the mnemonic representations of older adults can include: (i) recently activated but no-longer-relevant information; (ii) task-unrelated thoughts and/or prior knowledge elicited by the target information; and/or (iii) task-irrelevant information cued by the immediate environment.  This information is then automatically bound together with target information, creating cluttered memory representations that contain more information than do those of younger adults.

It's like trying to find something in a cluttered, disorganized attic.  Not only is it hard to locate what you're looking for, you get distracted by the other things you run across.  "Wow, it's been years since I've seen this!  I didn't even know this was up here!.... wait, what am looking for?"

I've noticed this exact problem in the kitchen.  I'm the chief cook in our family, and I love to make complex dinners with lots of ingredients.  I've found that unless I want to make a dozen trips to the fridge or cabinets to retrieve three items, I need to focus on one thing at a time.  Get a green pepper from the vegetable crisper.  Find the bottle of cooking sherry.  Go get the bottle of tabasco sauce from the table.  If I try to keep all three in my mind at once, I'm sure to return to the stove and think, "Okay, what the hell do I need, again?"

I wonder if this mental clutter is at the heart of my struggle with memorizing the hiragana characters in Japanese.  I've done at least a cursory study of about a dozen languages -- I'm truly fluent in only a couple, but my master's degree in historical linguistics required me to learn at least the rudiments of the languages whose history I was studying.  Could my difficulty in connecting the Japanese characters to the syllables they represent be because my Language Module is clogged with Old Norse and Welsh and Scottish Gaelic and Icelandic, and those all get in the way?

In any case, it's kind of a relief that I'm (probably) not suffering from early dementia.  It also gives me an excuse the next time my wife gets annoyed at me for forgetting something.  "I'm sorry, dear," I'll say.  "I'd have remembered it, but my brain is full.  But at least I remembered that the character yo looks like a yo-yo hanging from someone's finger!"

Nah, I doubt that'll work, and the fact that I remembered one of the Japanese characters instead of stopping by the store to pick up milk and eggs will only make it worse.  When I want to be sure not to forget something, I guess I'll have to keep making a list.

The only problem is then, I need to remember where I put the list.

***************************************

People made fun of Donald Rumsfeld for his statement that there are "known unknowns" -- things we know we don't know -- but a far larger number of "unknown unknowns," which are all the things we aren't even aware that we don't know.

While he certainly could have phrased it a little more clearly, and understand that I'm not in any way defending Donald Rumsfeld's other actions and statements, he certainly was right in this case.  It's profoundly humbling to find out how much we don't know, even about subjects about which we consider ourselves experts.  One of the most important things we need to do is to keep in mind not only that we might have things wrong, and that additional evidence may completely overturn what we thought we knew -- and more, that there are some things so far out of our ken that we may not even know they exist.

These ideas -- the perimeter of human knowledge, and the importance of being able to learn, relearn, change directions, and accept new information -- are the topic of psychologist Adam Grant's book Think Again: The Power of Knowing What You Don't Know.  In it, he explores not only how we are all riding around with blinders on, but how to take steps toward removing them, starting with not surrounding yourself with an echo chamber of like-minded people who might not even recognize that they have things wrong.  We should hold our own beliefs up to the light of scrutiny.  As Grant puts it, we should approach issues like scientists looking for the truth, not like a campaigning politician trying to convince an audience.

It's a book that challenges us to move past our stance of "clearly I'm right about this" to the more reasoned approach of "let me see if the evidence supports this."  In this era of media spin, fake news, and propaganda, it's a critical message -- and Think Again should be on everyone's to-read list.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Forever young

At 61 I'm reaching the age where I can't deny that I'm not young any more.  By and large, though, I've been lucky.  I now need bifocals -- more to read than to do anything else, but I wear them all the time because if I don't I'll lose them, yet another fun feature of aging.  I have mild high blood pressure (controlled by medication).  A few gray hairs and laugh lines.

But overall, I'm pretty fortunate.  It's a curious thing, though, why people seem to age at different rates, and (in the broader sense) why some species age faster.  It's a current hot topic in research; why (for example) do mice mostly age out at three or four years, dogs at age thirteen or fourteen (lower for some large breeds), cats at seventeen or so, horses by age thirty, and so on?  Despite improvement in human life expectancy because of better prevention and treatment of disease, scientists haven't been able to do much about aging itself; if you are diagnosed with heart disease, you'd have a better chance of surviving now than you would have a hundred years ago, but all of the attendant features of old age proceed at the same rate they always have.

One of the biggest mysteries about aging is why some animals seem to be resistant to it.  I'm not just talking about life expectancy; even though mice and humans have vastly different life spans, toward the end of their lives they're prone to the same things -- cardiac and circulatory problems, arthritis, eyesight and hearing loss, dementia.  It's just that with mice, that whole cycle is compressed by a factor of twenty-five.  More puzzling are the handful of animals that don't seem to age at all, at least not in the conventional sense; for example, there's a hydrozoan jellyfish, Turritopsis dohrnii, that cheats death by something almost like a Doctor Who-style regeneration; it transforms itself, down to the cellular level, to the youthful (polyp) stage, then starts over from there, rendering it effectively immortal if it doesn't die from other causes.

Jellyfish are, of course, a long way from humans evolutionarily (and therefore genetically).  Closer to us are the bizarre naked mole-rats (Heterocephauls glaber) of the deserts of Ethiopia and Somalia.  They've been the focus of a lot of study -- Chris Faulkes, of Queen Mary University of London, has been looking at their weird, almost ant-colony-style social structure, and says, "They just draw you in; they’re obviously really, really cute," which I find kind of mystifying, because to me they look like a penis with teeth.

But eye of the beholder, and all that sorta stuff.

What's weirdest about these odd rodents, though, is that unlike their more familiar cousins, they have life spans of forty or more years.  But this isn't a case of simply taking the years of life, with all of their attendant ills at the end, and adjusting it accordingly; naked mole-rats simply don't seem to get all the age-related disorders.  Cardiac and circulatory problems, arthritis, type-2 diabetes, and so on, just don't afflict them.  What exactly they do die of is still a bit of a mystery, because they seem to be just as vigorous at age 35 as they were at age 5.  "Naked mole-rats are a model of healthy aging," said Vera Gorbunova, of the University of Rochester, who has been studying how they accomplish this.

She and her colleagues have uncovered some unexpected results.  What's oddest is that their genetic biological clocks -- something that all mammals have, which are indicators of age regardless of overall health -- seem to keep track perfectly well.  It might make sense to surmise that a species who cheats aging so adroitly might be doing it by virtue of a broken biological clock, but that's not what's going on here.  They have seven molecular clocks that work as good indicators of age, and in fact, two of them are also found in humans (and work the same way).  An alternative theory -- one that's being researched -- is that they are better at protecting their epigenomes (the record of alterations made to an individual's genome during its lifetime), or at fixing damage to the DNA, but both are at this point only hypotheses.

Naturally, what people are wondering is whether any discoveries of how exactly the naked mole-rats are doing this could be applied to humans.  On the one hand, increasing our life spans dramatically would do no favors for our already overcrowded Earth; but I have to say, if I could improve my likelihood of healthy aging, I'd be the first in line.  I'm not really afraid of dying, but I am afraid of debility -- I'm one of those people who loathes having to be dependent on others for my care, so some of the degenerative diseases of old age absolutely scare the shit out of me.

We're a long way from that, though, probably long enough that it won't do me much good.  So I guess I'll have to continue relying on my good diet, exercise, and a family history of long-lived people to keep me going.  Even if we find out what the naked mole-rats are doing, transplanting that into a human is going to be a considerable, if not insurmountable, challenge.

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It's obvious to regular readers of Skeptophilia that I'm fascinated with geology and paleontology.  That's why this week's book-of-the-week is brand new: Thomas Halliday's Otherlands: A Journey Through Extinct Worlds.

Halliday takes us to sixteen different bygone worlds -- each one represented by a fossil site, from our ancestral australopithecenes in what is now Tanzania to the Precambrian Ediacaran seas, filled with animals that are nothing short of bizarre.  (One, in fact, is so weird-looking it was christened Hallucigenia.)  Halliday doesn't just tell us about the fossils, though; he recreates in words what the place would have looked like back when those animals and plants were alive, giving a rich perspective on just how much the Earth has changed over its history -- and how fragile the web of life is.

It's a beautiful and eye-opening book -- if you love thinking about prehistory, you need a copy of Otherlands.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Five dozen trips

Dear Skeptos...

After today I'm taking a quick break -- this will be my only post this week.  I'll be back on Monday, November 2.  Until then, please keep topic suggestions coming!

cheers,

Gordon

*********************************

Today is my sixtieth birthday.

I'm not a big believer in the significance of milestones, but this one seems to be pretty major.  Partly, it's my incredulity over turning sixty when I don't feel sixty.  Well, in some ways I do; I've got more aches and pains and minor physical issues than I used to.  Fortunately, at this point, nothing at all serious.  I've got some gray, especially in my facial hair, so I keep it trimmed really short to minimize the impact.  I have a few more wrinkles and laugh lines.  I need reading glasses (either that, or my conjecture that everyone is printing in smaller and smaller fonts is correct).  My stamina for running is less than it used to be.

Overall, though, I can't complain.  I've made it here relatively unscathed.

What sixty looks like

Part of that is good luck, and part is good genes.  I come from a family of long-lived people.  My parents both made it to 83, and my dad especially looked a consistent ten years younger than he actually was, pretty much his whole life.  His mom, my beloved Grandma Bertha, lived to 93, and her eccentric Aunt Clara died at 101.  (Great Aunt Clara was almost completely blind during the last ten years of her life, but still walked daily around her home town of Wind Ridge, Pennsylvania with her red-tipped cane.  The story is that she made a point of whapping people she didn't like with her cane as she passed them.  "Accidentally."  Just showing that irascibility runs in my father's family as well as longevity.)

So as far as genetics goes, I got dealt a pretty good hand.

I also attribute some of it, though, to the fact that I still have the sense of humor of a twelve-year-old.  Nothing keeps you young like retaining your ability to laugh at fart jokes.

Looking back, it's been a wild ride.  I've come a long way in sixty years, both literally and figuratively.  I've been lucky enough to have the opportunity to travel to exotic places like Ecuador and Trinidad and Malaysia.  I live in upstate New York, which I would put in contention for the most beautiful place in the world.  I have two sons I'm proud of.  Despite off-the-scale shyness and social anxiety I'm happily married to the love of my life.  I'm a published author with fifteen books to my name.  I just retired a couple of years ago after a 32-year career teaching science to teenagers, a vocation that was some combination of challenging, fun, frustrating, and exhilarating -- truly a job where you never know what's going to happen next.  With the support of family and friends, two years ago I finally came out publicly as bisexual, shedding decades of shame and fear and finally stepping into the light and saying, "This is who I am."  I've learned a lot about myself and others, especially the deep, aching truth of what a family friend told me when I was six: "Always be kinder than you think you need to be, because everyone you meet is fighting a terrible battle that you know nothing about."  Through it all, I've come out mostly happy, mostly healthy, and entirely glad to be where I am.

I am an incredibly lucky man.

Still, it's a little mind-boggling that I've made five dozen trips around the Sun.  It's hard to fathom that it's been that long.  When someone says "twenty years ago," I immediately think, "1980?"  No, that's forty years ago.  Twenty years ago is 2000.  Today's twenty-year-olds were infants when 9/11 happened.  So many of the things I think of as high-magnitude historical events -- the explosion of the Space Shuttle Challenger, the start of the Gulf War, the Exxon Valdez oil spill, the launch of the Hubble Space Telescope, the development of the World Wide Web and email, the breakup of Yugoslavia and the siege of Sarajevo, the Oklahoma City bombing, the signing of the Good Friday Agreement that officially ended the Irish "Troubles" -- all happened before today's twenty-year-olds were born.

I can't fool myself.  I haven't been young for quite some time.  It brings back memories of my grandma, then about eighty, dropping into her favorite rocking chair with a groan, then cocking an eyebrow at me and saying, "You know, Gordon, I'm no spring chicken any more."  I'd usually grin and say, "Grandma, when were you a spring chicken?"  To which she'd retort something like, "Last Thursday, you little pipsqueak.  Now fix me a martini."  And we'd both crack up.

Then I'd fix her a martini.

That's the kind of eighty-year-old I want to be.

I guess there's no avoiding aging, although I do think a lot of it boils down to attitude.  You can't escape the physical stuff completely, although you can ameliorate it by staying active; I'm glad I'm still a runner, and I suspect that I'd be in way worse shape than I am if I'd become sedentary.  But I'm damned if I'll let it get me down.  I remember a friend of mine turning sixty, and he went into a serious depression -- it was so much harder than fifty, he said, "because there's no doubt you're past halfway.  Some people make it to a hundred, but almost no one makes it to a hundred and twenty."

Which might be true, but it's not going to stop me from trying.

So anyhow: happy birthday to me.  Despite my friend's hang-dog attitude, here's to the next five dozen trips.  Maybe my attitude is a little like the guy who fell off the roof of a skyscraper, and as he passes the twentieth floor, someone yells out of a window at him to ask how he's doing, and he shrugs and says, "So far, so good."

But it's better than the alternative.  Much better to relax, enjoy the view, and have a martini.

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Have any scientifically-minded friends who like to cook?  Or maybe, you've wondered why some recipes are so flexible, and others have to be followed to the letter?

Do I have the book for you.

In Science and Cooking: Physics Meets Food, from Homemade to Haute Cuisine, by Michael Brenner, Pia Sörensen, and David Weitz, you find out why recipes work the way they do -- and not only how altering them (such as using oil versus margarine versus butter in cookies) will affect the outcome, but what's going on that makes it happen that way.

Along the way, you get to read interviews with today's top chefs, and to find out some of their favorite recipes for you to try out in your own kitchen.  Full-color (and mouth-watering) illustrations are an added filigree, but the text by itself makes this book a must-have for anyone who enjoys cooking -- and wants to learn more about why it works the way it does.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Tree of life

One of my favorite time wasters is the site Quora, where you can ask any question you like and get (if you're lucky) dozens of answers from people who know.  Of course, being a site where the content comes from everyone and anyone, there are a good many dumb questions and even more dumb answers, but by and large, the site is fairly entertaining,

Having answered a couple of biology-related questions in the past, the site's algorithm now throws a lot of biological questions my way when I sign on, and just yesterday I was given an interesting one: do plants have life spans -- do they age and die?  As it so happens, I've read a bit (only a smattering, I'm hardly an expert) on this subject, and there actually is senescence -- age-related degradation -- in at least some species of plants, and that's not even counting true annuals which only live one year.

Yellow birch trees, for example, usually don't make it past forty or fifty years, quaking aspens sometimes not even that much.  Silver maples start to fall apart, often rotting from the inside out, when they're in their seventies and eighties; sugar maples can easily make it to 150 years.  At the upper end of the scale are trees like redwoods, which get into the thousands of years old.  The oldest known tree is a bristlecone pine in the White Mountains of California, which a trunk core showed to be 5,065 years old.

Consider it.  When Jesus walked the Earth, this tree was already three thousand years old.

In one of those weird synchronicities, yesterday afternoon -- only a couple of hours after I answered the question on Quora -- I stumbled upon a paper in Proceedings of the National Academy of Sciences that looked at the phenomenon of longevity in trees, more specifically in the strange Gingko biloba or "maidenhair tree," the only living species in the entire phylum Ginkgophyta.  It's native to southern China, and had been cultivated locally there for centuries for its beautiful symmetrical shape, graceful leaves, and incredibly smelly fruit that are used medicinally.  It was brought to Europe about three hundred years ago, and now is grown all over the world -- a remarkable comeback for a plant that was truly a living fossil.

Ginkgoes are amazingly long-lived, some specimens in China and Japan exceeding three thousand years in age.  The researchers collected tissue from a variety of ginkgo trees, from age three on up, and looked for the markers of senescence.

What they found was fascinating.

[Image licensed under the Creative Commons Jean-Pol GRANDMONT [CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)]]

Dying leaves at mid-autumn showed lots of activation of aging-related genes.  On a leaf-by-leaf basis, the tree was doing exactly what animals do; experiencing metabolic slowdown, lowered immunity to infection, and structural degradation.  But the tree as a whole showed no such tendencies.  Genes related to aging showed no greater expression in old trees than they did in young trees.

There were differences, of course, primarily in genes controlling growth rate.  Young trees grow faster than old ones.  But it seems like if you're a gingko tree, you get to be your adult size, and then you just kind of go into stasis -- for thousands of years.

To quote Howard Thomas, botanist at Aberystwyth University (who was not involved in the ginkgo study), "The default condition for plants is immortality."

How this is controlled genetically is still poorly understood.  Hell, we don't even know how it's controlled in ourselves; it's likely to have something to do with the telomeres, the "end caps" on chromosomes that shorten with each cell division and thus act as a kind of molecular clock that keeps track of the age of the organism.  It's almost certainly not that simple, of course, and there are probably contributions to the aging process from cumulative DNA damage, epigenetic effects, metabolism and diet, and slowing of the immune system.  It's currently a huge area of research, because (face it) few of us are all that fond of the idea of aging.  I've got a great many more gray hairs, laugh lines, and backaches than I did even ten years ago, and if I could somehow reverse all that I'd be all for it.

An immortality pill is probably a long, long way off, enough that I pretty certainly won't be here to take advantage of it.  And whatever the mechanisms are for controlling aging in humans, they're not going to be similar enough to plants that the current research will give us much hope in that direction.

But given how the woo-woos think, expect a huge surge in sales for Ginkgo biloba tablets claiming that if you take them every day, you won't age.  Same as the craze for shark cartilage tablets a few years ago when the claim (which turns out to be false anyway) that sharks never get cancer convinced people that the way to avoid cancer was to swallow shark bits in pill form.

Me, I'm just interested in the research because it's kind of cool.  If this or other studies uncovers a solution to the aging problem, that'd be cool, but for now I think I'll just admire this lovely tree -- and marvel at its ability to live essentially forever.

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This week's Skeptophilia book of the week is scarily appropriate reading material in today's political climate: Robert Bartholomew and Peter Hassall's wonderful A Colorful History of Popular Delusions.  In this brilliant and engaging book, the authors take a look at the phenomenon of crowd behavior, and how it has led to some of the most irrational behaviors humans are prone to -- fads, mobs, cults, crazes, manias, urban legends, and riots.

Sometimes amusing, sometimes shocking, this book looks at how our evolutionary background as a tribal animal has made us prone all too often to getting caught up in groupthink, where we leave behind logic and reason for the scary territory of making decisions based purely on emotion.  It's unsettling reading, but if you want to understand why humans all too often behave in ways that make the rational ones amongst us want to do repeated headdesks, this book should be on your list.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!] 

Medical care, serial dilution, and mathematical horses

It's been a while since we've seen a new salvo from the homeopaths, but I knew this did not mean they'd retreated in disarray.  After all, a belief in pseudoscientific woo-woo quackery means never having to say you're sorry.

The most recent news from the world of homeopathy comes from an online magazine called Clever H.  This is in many ways an unfortunate choice of names.  It immediately reminded me of "Clever Hans," a horse back in 1907 whose owner claimed he could do arithmetic.  Of course, the horse could do no such thing, but was shown by German psychologist Oskar Pfungst to be receiving cues from its owner.  Once the owner was taken off stage, suddenly Clever Hans lost his phenomenal ability to do calculations.

Clever Hans and his owner [Image is in the Public Domain]

So calling the magazine a name that recalls a debunked false claim isn't so much unflattering as it is ironic.  Apparently unaware of this, the writers are boundless in their enthusiasm, subtitling Clever H as "The Mag by Homeopaths, for Homeopaths, With the Patient in Mind!"  The article that caught my attention was called "The Anti-Aging of Homeopathic Cell Salts," which I at first thought meant they'd discovered a way to keep salt from aging.

Which, as far as I've heard, is not really a big problem.

But that isn't what the article's about.  It claims that they've discovered some chemicals ("cell salts") that can prevent, or even reverse, aging.  The authors write:

Tissue Salts are an off shoot of homeopathy and are vital elements that correspond to the same minerals our cells are made of.  These “vital elements” will nourish and rebuild your cells...   [A] homeopathic treatment that can be helpful in slowing the aging process and reducing the early signs of aging is a homeopathic detox of the liver, kidney and lymphatic system.  This will stimulate your body to function better.  A noticeable difference will be seen on the skin’s appearance and even aches and pains will improve.  When the lymphatic system is functioning at its best, weight loss and cellulite will be in control and the immune system will be functioning optimally.

Equipped with such homeopathic anti-aging secrets, the aging process can be slowed and life can be lived to the fullest beyond the days of youth.

Now, at the age of 58, no one would be happier than me to find there was a way to reverse aging.  (Physical aging, I mean.  My emotional age kind of plateaued around age 13, which is why I still laugh at fart jokes.)  On the other hand, I'm not so fond of the gray hair, wrinkles, and miscellaneous aches and pains, and would thrilled if I could return to the physique I had when I was 25.

What Clever H says we should do is take the homeopathic concoctions "calc fluor," "calc phos," and "kali phos," because all of these are valuable "cell salts" that will have the effect of restoring your youth.  Oh, and also "nat mur," which is a "water distributor."  Which, I suppose, is better than having water pool in our feet, or something.

So I did some research -- if you can dignify it by that name -- and found out that "calc fluor" is useful for treating hemorrhoids, "calc phos" restores health after an injury, "kali phos" is good for stress, and "nat mur" keeps you from drying out.  "Nat mur," I also found out, was made from plain old salt, so I was curious as to why they were making such a big deal about it.  In searching for an answer I stumbled upon a page about "nat mur" on the site of the British Homeopathic Organization, which had some information that was puzzling, to say the least:

The higher organisms, the mammals, require sodium chloride in comparatively large amounts.  It is clear that as life evolves to higher forms, and the faculties of perception and feeling unfold, the role of sodium chloride in psychological and biological functions becomes increasingly important.  The active secretion of salt through the urine, sweat and tears appeared in parallel with the development of feeling and the tender emotions.

So I'm supposed to develop tender emotions when I'm taking a piss?  Or am I missing some vital piece of the argument, here?

We also find out there are "nat mur" personalities, which are characterized by harshness, resentment, and lack of demonstrative emotions.  Because of the ocean or something.

 But back to the Clever H page, wherein we find that the recommended concentrations of all of these "remedies" are between "6x" and "30x."  For those of you who don't know how homeopathic "remedies" are produced, allow me to explain that each "x" represents a 1-in-10 dilution.  So a 6x dilution would have 1 part of the original substance dissolved in 1,000,000 parts of some inert substance like water or a sugar pill.  So that's pretty dilute, but it's nothing like a 30x dilution, which is 1 part of the original substance dissolved in 1,000,000,000,000,000,000,000,000,000,000 parts of inert substance.

Which for most of us qualifies as "really fucking dilute," but those of you who know some chemistry might recognize that this dilution far surpasses Avogadro's Limit -- because once you have done a 1-in-10 serial dilution 23 times, you have (on average) one molecule of the original substance left.  Any further dilution, and you essentially have nothing there but the inert carrier.

Not that the original substance does what the homeopaths say it does in the first place.  But considering that they claim that the more dilute a substance is, the stronger it is, I'm not sure we should be splitting scientific hairs, here.

If you paw around the Clever H site, you find the following disclaimer:

All content on this website is intended as an adjunct to, not a substitute for professional homeopathic and/or medical care. 

No publication of Clever H. or its sub-pages should be interpreted as a means of diagnosis or treatment for any disease or condition, and the articles published at Clever H. by no means claim completeness of information. 

For a medical diagnosis or treatment a licensed medical professional should be consulted. Homeopathic treatments should only be undertaken under direct guidance and care of a professionally trained Health Care Professional specialized in the services described.

Maybe it's just me, but "A noticeable difference will be seen on the skin’s appearance and even aches and pains will improve.  When the lymphatic system is functioning at its best, weight loss and cellulite will be in control and the immune system will be functioning optimally" sure sounds like a recommendation for a "treatment of [a] disease or condition."

I keep hoping that the homeopaths and other purveyors of pseudo-medical quackery will be so widely known for what they are that they'll go out of business, but (much as it pains me to admit it) homeopathic "remedies" are still on the shelves of our local pharmacy.  Including some that are 30x dilutions (or even more dilute, and therefore stronger).  This means that people are buying them, and using them in the hopes of treating conditions for which they should be seeking out legitimate medical care.  Bringing me back once again to the site What's the Harm -- wherein you will find that a lack of critical thinking skills, with regards to your own health, can be very, very dangerous.

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This week's Skeptophilia book recommendation is a classic: Richard Dawkins's The Blind Watchmaker.  This book is, in my opinion, the most lucid and readable exposition of the evolutionary model ever written, and along the way takes down the arguments for Intelligent Design a piece at a time.  I realize Dawkins is a controversial figure, given his no-quarter-given approach to religious claims, but even if you don't accept the scientific model yourself, you owe it to yourself to see what the evolutionary biologists are actually saying.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]

A switch for aging

CRITICAL THINKING COURSE AVAILABLE STARTING TODAY!

I have an exciting announcement -- today, I'm launching a course called Introduction to Critical Thinking through Udemy!  It includes about forty short video lectures, problem sets, and other resources to challenge your brain, totaling about an hour and a half.  The link for purchasing the course is here, but we're offering it free to the first hundred to sign up!  (The free promotion is available only here.)  We'd love it if you'd review the course for us, and pass it on to anyone you know who might be interested!

Thanks!

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I, and many of my friends, are of That Certain Age where we have started getting such awesome physical symptoms as graying hair, wrinkles, arthritis, forgetfulness, and the necessity of either wearing reading glasses or getting arm extensions.  I'm not the sort that will let being 57 (or any other age) slow me down if I can help it, but there's no denying that I don't feel as young as I did twenty (or even five) years ago.

So any time I see an article on the biology of life span, my ears perk up.  I'm hopeful that there will eventually be medical ways to extend healthy life span (sure would be nice if it happened soon...), but to get there, we need to understand how aging actually works.  And a new piece of research out of the University of Minnesota has given us another clue.

Geneticists Adam McLain and Christopher Faulk were interested in a feature of the genetics of all eukaryotes (life forms that have nuclei -- therefore, every common organism with the exception of bacteria) called a promoter.  To see where this is going, a brief biology lesson.

You can think of genes as recipes.  They are a set of instructions that, speaking in the A/T/C/G language, spell out the directions for building proteins.  Many of those proteins then go on to influence other genes, creating a cascade of activity that we collectively call "development."

Promoters are, in a way, the director of the orchestra.  Or -- a more apt analogy -- they're like a set of switches.  The promoters are not part of the recipe itself; they have instead the critical job of pointing out where the recipe is, making sure that it's switched on (or off) at the right time, and regulating how fast the end product is produced.  Errors in a promoter region are usually devastating -- one of the milder examples is genetic lactose intolerance, where faulty promoter turns off the gene that produces lactase, the enzyme that digests lactose, leading to an inability to drink milk after the age of three or four (and some pretty nasty symptoms if you do).

[Image is in the Public Domain]

So promoters are critical to genes, not only turning them on or off in the right sequence, but making sure that the right amount of the protein is made in the right tissue type.  This importance means they're what geneticists call "highly conserved sequences" -- things go so badly awry when they malfunction that there are few mutational differences between promoters in different species.  What McLain and Faulk wondered is if promoter activity might have something to do with the rate of aging, so they set out to compare those small number of mutational differences between species that have generally short life spans (such as mice) and those that have generally long life spans (such as elephants).

What they looked at are called CpG sites -- areas high in the bases cytosine and guanine (and in which they occur right next to each other), which are found in promoters and are targets for methylation, a process that turns promoters off more or less permanently.  And what they found is that the density of CpG sites positively correlates with average age at death.

Which is pretty amazing.  The authors write:

As vertebrates age, the epigenomic pattern of DNA methylation degrades, with the highly methylated CpG sites gradually becoming demethylated, while CGIs increase in methylation.  Therefore, DNA methylation becomes dysregulated as a function of aging and high CpG density may delay or buffer specific regions from age-related changes.  Some gene exons have undergone accelerated evolution in long-lived species as their protein function is under selection.  However, unlike coding sequences, promoter regions alter gene expression, not protein function, so different species can regulate expression without altering the protein function.  Within promoter regions the rapid mutation of CpG sites and their function in epigenetic gene expression make them prime targets for natural selection.  We chose CpG site density because density alone is sufficient to predict methylation level.  Since methylation degrades over an individual's lifespan, we reasoned that selection for long lifespan may act not only on gene coding regions but on promoter regions.  This selection would change promoter CpG density for genes whose expression must be more tightly regulated to allow for longer lifespan.

So methylation, connected to the presence (and number) of CpG sites, is tightly connected to life span; as you age, the regulation of methylation starts to fall apart, deactivating genes that should be active and activating genes that should be turned off.  Species whose promoters have a higher density of CpG sites regulate methylation more tightly -- and age more slowly!

When I got to the punchline of their paper, I was a little stunned.  It's astonishing that life span could be controlled by something that simple (okay, the concept isn't simple, but the connection between CpGs and aging rate is pretty straightforward).  The next question, of course (especially those of us who are rapidly approaching geezerhood) is whether there's a way to affect the process of methylation -- preserving its ability to regulate gene expression, and (presumably) slowing down the aging process.

All of which is far beyond the scope of this study.  But still, it's an intriguing prospect, whether or not it ever becomes feasible in practice.  Me, I hope it does, and I hope it's soon.  Because I've about had it with gray hair, creaky joints, and entering a room only to immediately forget why I'm there.

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This week's featured book is a wonderful analysis of all that's wrong with media -- Jamie Whyte's Crimes Against Logic: Exposing the Bogus Arguments of Politicians, Priests, Journalists, and Other Serial Offenders.  A quick and easy read, it'll get you looking at the nightly news through a different lens!

Permafrost permayouth

You might have heard about people consuming pills of dried shark cartilage as nutritional supplements.  They're still widely available, in fact.  It's supposed to be anti-carcinogenic.  Why, you might ask, did people get this idea?

Because, the purveyors of shark cartilage pills say, sharks don't get cancer.  So if you grind up shark parts and consume them, you won't get cancer either.

There are just two problems with this practice:

• Sharks actually do get cancer, something that has been known since at least 1908.
• Shark cartilage has been tested and found to have no beneficial therapeutic value whatsoever.  It is, however, kind of critical for the shark itself, and the practice of killing sharks for their cartilage has led to widespread decline in sharks in many parts of the world.

This did not stop two of the most prominent cartilage shark spokespeople, I. William Lane and Linda Comac, from writing a book called Sharks Don't Get Cancer.  When the book was completely trashed by scientists and other reviewers, Lane responded by writing a second book four years later called Sharks Still Don't Get Cancer.

His publisher wisely recommended that Lane eliminate the subtitle he was planning to use, which was So Take That Nyah Nyah Nyah Nyah pfffttptbtbtbtbtb.

As usual, we have people who aren't letting little things like evidence and facts stand in the way of their claim.  You can still buy shark cartilage pills in many pharmacies, including a brand called, I kid you not, "BeneFin."

I bring all this up because yesterday I ran across a story about a woman who is doing something even stupider than consuming shark cartilage to prevent cancer; she is injecting herself with bacteria so she won't age.

It's not just ordinary, garden-variety bacteria, either.  These are bacteria that had been frozen in the permafrost of Siberia for, by some estimates, 3.5 million years, and now have been resuscitated by the thaw.  A Russian professor of geology named Anatoli Brouchkov noticed that the Yakut people who live in the area have a reputation for long lifespans, so he decided that (of course) it had to be because they were drinking melted permafrost water that had the bacteria in it.

Couldn't be genetics, or diet, or anything.

So he treated some plants, fruit flies, and mice with the bacteria, which has been dubbed "Bacillus F."  Brouchkov that they "seemed to have a rejuvenating effect," although gives no details about how he knew.  How do you distinguish between a rejuvenated houseplant and a tired, listless one?  Do non-rejuvenated fruit flies fly about in a dejected fashion?

Be that as it may, Brouchkov is certain enough of his claim that he's drinking water with Bacillus F in it himself.  But an actress who calls herself "Manoush" has gone a step further; she is now injecting herself with the bacteria.

Manoush, best known for such A-list blockbusters as Zombie Reanimation, The Shrieking, Philosophy of a Knife, and The Turnpike Killer, says she started taking the bacteria because like many of us, she's not so fond of the idea of getting old.  "Aging is a disease," she says.  "It is a genetic flaw to me.  Even as a teenager I could never accept the concept of getting older one day.  I don’t care what people think. I will stop at nothing to look and feel younger.  Nothing."

Which, I think we could all agree, would leave us with no option other than injecting 3.5 million-year-old Siberian permafrost bacteria directly into our bodies.

Manoush is absolutely convinced she's now aging backwards.  Me, I'm not sure.  I'm not fond of the gray hair, stiff joints, and crow's feet I've gotten in the past few years, but I don't think the answer is to jump on some loopy idea about anti-aging bacteria.  In fact, injecting bacteria into yourself is kind of a bad idea in general; perfectly normal, ordinary skin bacteria become a serious problem if they get into your bloodstream.  A friend of mine's father, in fact, almost died of a Staphylococcus aureus infection when his thumb got skewered by a rose thorn.

Staphylococcus aureus, I should point out, is a ubiquitous part of our skin flora.  On the surface of your skin, it's harmless.  Inside you, it can result in blood sepsis, which is a quick and spectacularly nasty way to die.

Staphylococcus aureus [image courtesy of the National Institute of Health]

So as much as I'd like perpetual youth, I'm not going to get in line behind Manoush for my bacteria injection.  I'll put up with the gray hair, which I'm told makes me look "distinguished," which isn't as good as "drop-dead sexy," but I guess I'll deal.