stop buying cheap-ish pseudo-generic drugs from Walgreens, Rite-Aid, and Duane Reade and start buying really cheap true generics. As you might know, Benadryl (available at Walgreens.com for $5.29 for a box of 24 capsules) and Wal-dryl ($3.99 / 24 capsules) are otherwise known as “25 mg. of diphenhydramine HCI.” Compare [with the true generic available at Amazon]. Yes, that is 400 tablets containing 25 mg. of diphenhydramine HCI, for about $10 when you factor in shipping.
20% of Nature readers use cognitive enhancers to improve their focus, concentration, or memory. Among those who choose to use, methylphenidate was the most popular agent: 62% of users reported taking it. Modafinil was taken by 44% of users and beta blockers by 15%. Many of the subjects were using more than 1 drug
2009-01-21: cognition-dulling drugs and cures for resentment, envy, or union-organizing may also serve to enhance workplace efficiency. 2009-05-07: it’s only a war on drugs if the drug in question makes you stupid
If I drink a cup of coffee, I (seemingly) think a bit faster. We call this tradition. If I take a modafinil I (measurably) think a bit faster. We call this cheating.
2010-04-28: And some philosophical considerations:
Cognitive enhancement takes many and diverse forms. Various methods of cognitive enhancement have implications for the near future. At the same time, these technologies raise a range of ethical issues. For example, they interact with notions of authenticity, the good life, and the role of medicine in our lives. Present and anticipated methods for cognitive enhancement also create challenges for public policy and regulation.
2015-02-19: Any progress in telling which, if any, nootropics actually work, is welcome.
The research, published in open-access Frontiers in Systems Neuroscience, uses an algorithm that maps expression data onto signaling pathways. The collective pathways and their activation form a “signaling pathway cloud” — a biological fingerprint of cognitive enhancement. Drugs can then be screened and ranked based on their ability to minimize, mimic, or exaggerate pathway activation or suppression within that cloud.
But why should there be smart drugs? Popular metaphors speak of drugs fitting into receptors like “a key into a lock” to “flip a switch”. But why should there be a locked switch in the brain to shift from THINK WORSE to THINK BETTER? Why not just always stay on the THINK BETTER side? Wouldn’t we expect some kind of tradeoff?
Piracetam and nicotine have something in common: both activate the brain’s acetylcholine system. So do 3 of the most successful Alzheimers drugs: donepezil, rivastigmine, and galantamine. What is acetylcholine and why does activating it improve memory and cognition?
Mind-expansion may soon become big business. Even though the drugs have been developed to treat disease, it will be hard to prevent their use by the healthy.
The overall positive effect of modafinil over placebo across all cognitive domains was small and significant (g = 0.10; 95% confidence interval, 0.05-0.15; P < 0.001). No significant differences between cognitive domains were found. Likewise, no significant moderation was found for modafinil dose (100 mg vs 200 mg) or for the populations studied (psychiatric vs nonpsychiatric).
The subgroup who used Zembrin reported a mean effectiveness of 6.88, which beats out modafinil to make it highest on the list. After ad hoc Bayesian adjustment, it was 6.72, second only to modafinil as the second most effective nootropic on the list. This really excites me – I’ve felt like Zembrin was special for a while, and this is the only case of a newer nootropic on the survey beating the mainstays. And it’s a really unexpected victory. The top 8 substances in the list are all either stimulants, addictive, illegal in the US, or all 3. Zembrin is none of those, and it beats them all.
The Last Psychiatrist: How To Take Ritalin Correctly is a great little essay on how to use Ritalin for studying. It is great not because of any particular advice, but because it demonstrates how we ought to approach the use of cognition enhancers. Just swallowing them and expecting mental perfection will not work; like all drugs there is an interaction between set and setting, in particular what task we are doing. This means we need to know what enhancers work for what kind of activity, and perhaps tailor the activity to the enhancer slightly. In a culture where enhancers are routinely used this kind of advice would be normal studying technique advice. As for the exact advice, it seems sound from my reading, although I can’t claim to understand the attention metaphors very well.
how society slowly kills old laws without actually taking them off the books
Our parents and grandparents banned drugs, but the current generation is re-legalizing them. That’s why Rush Limbaugh, as a drug user, is in a sense a symbol of our times.
the presence of jerks during rest in the gray whale, taken together with our previous data on 3 species of dolphins, allows us to suggest that short episodes of REM do exist in Cetaceans
the absence of orexin A appears to cause narcolepsy. That finding pointed to a major role for the peptide’s absence in causing sleepiness. It stood to reason that if the deficit of orexin A makes people sleepy, adding it back into the brain would reduce the effects
Franco Banfi was following this pod of sperm whales when the giants suddenly seemed to fall into a vertical slumber. These massive marine mammals spend 7% of their time taking short (6- to 24-minute) rests in this shallow vertical position. Scientists think these brief naps may be the only time the whales sleep.
Recent research has demonstrated the effectiveness of short light pulses to alter circadian phase during sleep in human subjects. 2-millisecond light flashes administered during sleep penetrate the eyelids and change circadian timing without interfering with sleep quality. Due to the properties of the retinal cells that transduce light information to the circadian system, these millisecond light flashes match or exceed the effectiveness of continuous bright light to shift circadian phase. More than 1.5 hours of phase shift can be generated with just over 1 total second of light exposure during 1 hour. LumosTech is developing a smart sleep mask that contains bright LEDs able to emit a range of millisecond light pulses at several frequencies. Light timing is controlled by a smartphone app that uses a proprietary algorithm to calculate the frequency and duration required for shifting circadian phase. The light stimulation is delivered during sleep in conjunction with a mathematical model of circadian phase to advance or delay sleep cycles. The mask contains additional LEDs that provide a red-wavelength dawn simulator to stimulate the release of cortisol; this promotes alertness and enhances mood immediately after wakeup.
Our brain profoundly alters its behavior and purpose, dimming our consciousness. For a while, we become almost entirely paralyzed. We can’t even shiver. Our eyes, however, periodically dart about behind closed lids as if seeing, and the tiny muscles in our middle ear, even in silence, move as though hearing. We are sexually stimulated, men and women both, repeatedly. We sometimes believe we can fly. We approach the frontiers of death. We sleep. Around 2.35 ka BP, Aristotle wrote an essay, “On Sleep and Sleeplessness,” wondering just what we were doing and why. For the next 2300 years no one had a good answer. In 1924 German psychiatrist Hans Berger invented the electroencephalograph, which records electrical activity in the brain, and the study of sleep shifted from philosophy to science. It’s only in the past few decades, though, as imaging machines have allowed ever deeper glimpses of the brain’s inner workings, that we’ve approached a convincing answer to Aristotle.
An organized tide of brain waves, blood and spinal fluid pulsing through a sleeping brain may flush away neural toxins that cause Alzheimer’s and other diseases.
2020-11-10: Evening home lighting adversely impacts the circadian system and sleep
nearly 50% of homes had bright enough light to suppress melatonin by 50%, but with a wide range of individual responses (0–87% suppression for the average home). Greater evening light relative to an individual’s average was associated with increased wakefulness after bedtime. Homes with energy-efficient lights had 2x the melanopic illuminance of homes with incandescent lighting. Home lighting significantly affects sleep and the circadian system, but the impact of lighting for a specific individual in their home is highly unpredictable.
What, then, does sleep do in the absence of a brain? Raizen suspects that at least for some animals, sleep has a primarily metabolic function, allowing certain biochemical reactions to take place that can’t happen during waking hours. It may divert the energy that would be used by alertness and movement into other processes, ones that are too costly to take place while the animal is awake. For example, C. elegans seems to use sleep to enable the growth of its body and support the repair of its tissues. In sleep-deprived hydras, the cell divisions that are part of everyday life are paused. Something similar has been seen in the brains of sleep-deprived rats and in fruit flies. Managing the flow of energy may be a central role for sleep.
All of this begs the question of how the human brain deals with overfitting. Our day-to-day experience can be hugely repetitive, so how does the brain generalize from these singular experiences to other situations?
The human brain prevents overfitting by dreaming. Dreaming evolved specifically to deal with this problem, which is common to all neural networks. If this theory is correct, it answers one of the great unsolved problems in neuroscience: why we dream at all.
When Rößler recorded 34 sleeping spiderlings, she found that their twitches were accompanied by unmistakable eye-tube movements that did not happen during other phases of sleep. “It’s beautiful. I mean, it’s crazy. It immediately makes a sleep researcher think about rapid eye movement sleep”. Dreaming offers an entry point into questions of awareness in other animals: it is difficult to imagine that even a simple dream is possible without something like an ego or an “I” experiencing it, he adds. So if spiders dream, it might mean that we start talking about spiders having something like a minimal self.
The brain uses REM sleep to “learn” the body. You wouldn’t think that the body is something a brain needs to learn, but we aren’t born with maps of our bodies; we can’t be, because our bodies change by the day, and because the body a fetus ends up becoming might differ from the one encoded in its genome. “Infants must learn about the body they have. Not the body they were supposed to have.”
As a human fetus, you have 9 months in a dark womb to figure out your body. If you can identify which motor neurons control which muscles, which body parts connect, and what it feels like to move them in different combinations, you’ll later be able to use your body as a yardstick against which to measure the sensations you encounter outside. It’s easier to sense food in your mouth if you know the feeling of a freely moving tongue; it’s easier to detect a wall in front of you if you know what your extended arm feels like unimpeded. In waking life, we don’t tend to move only a single muscle; even the simple act of swallowing employs some thirty pairs of nerves and muscles working together. Our sleep twitches, by contrast, are exacting and precise; they engage muscles one at a time. Twitches “don’t look anything like waking movements. They allow you to form discrete connections that otherwise would be impossible.”
The theory turned the rationale for REM paralysis on its head: the paralysis isn’t there to stop the twitches but to highlight them. It’s a process that’s most important in infancy, but this might continue throughout our lives, as we grow and shrink, suffer injuries and strokes, make new motor memories and learn new skills. Blumberg plays the drums, and, when he learns a new rhythm, he wonders whether sleep is involved. “You struggle and struggle for several days, then one day you wake up and start playing and boom—it’s automatic. Did sleep play a role in that? If I had been recording my limb movements, would I have seen something interesting? That keeps me up at night.”
While they were sleeping, participants were repeatedly asked to frown or smile. All of them responded accurately to at least 70% of these prompts.
Overall response rates were higher for all participants during REM (rapid eye movement) sleep, when the deepest sleep occurs but the brain remains quite active, than during other sleep stages.
Unlike (soap and other) traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria. Alcohol-based hand sanitizers are just about as effective against germs as soap and water. They’re also easier on your skin than hand-washing, and unlike antibacterial soaps, they don’t breed antibiotic-resistant superbacteria.
The bottom line is that you shouldn’t live in fear of high-traffic surfaces. This type of contact simply isn’t the way people get sick.
This new resistance pattern has been reported in many different types of bacteria compared to previously and 10% of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials.
A lot of people have had similar ideas to this one, based on the fact that the overwhelming majority of bacteria in any given environmental sample can’t be readily cultured. These organisms may well be able to produce useful antibiotics and other natural products, but how will you ever be able to tell if you can’t fish any of them out? Using this on a soil sample from Maine and leaving the chip in situ for a month, a number of colonies formed. These were tested for their ability to grow outside the device in fermentation broth, and extracts of these were tested against pre-grown lawns of an S. aureus strain to look for useful antibiotic activity. Lo and behold, one extract cleared out a large spot – it turned out to come from a newly described bacterium (Eleftheria terrae, provisionally). The compound present has been named teixobactin, and here it is. So how useful is the compound? It’s active only against gram-positive organisms, which is too bad, because we could really use some new gram-negative killers (their cell membranes make them a tougher breed). But the mechanism of action turns out to be interesting: studies of S. aureus with labeled precursors showed that teixobactin is a peptidoglycan synthesis inhibitor, but extended exposure and passaging did not yield any resistant strains. That’s close to impossible if an antibiotic is binding a particular protein target – stepping on the selection pressure will usually turn up something that evades the drug. When you don’t see that, it’s often because there’s some nonspecific non-protein-targeted mechanism, which can be problematic, but teixobactin isn’t toxic to eukaryotic cells in culture (and has a favorable tox profile in mice as well). It turns out that it binds to some of the peptidoglycan precursors, lipid II and lipid III. Vancomycin has a similar mechanism (binding to lipid II), but teixobactin has a wider spectrum of activity against lipid II variants (and lipid III as well). This mechanism makes developing resistance not so straightforward – the selection pressure is more of a bounce shot than a direct hit.
we seem willing to pay $100K or more for cancer drugs that cure no one and at best add weeks or a few months to life. We are willing to pay 1$0Ks for knee surgery that, at best, improves function but is not lifesaving. So why won’t we pay $10K for a lifesaving antibiotic?
2015-03-31: Medieval salve kills MRSA. Impressive! Not all ancient medical knowledge is homeopathic nonsense.
Take cropleek and garlic, of both equal quantities, pound them well together… take wine and bullocks gall, mix with the leek… let it stand 9 days in the brass vessel
So goes a 1000-year-old Anglo Saxon recipe to vanquish a stye, an infected eyelash follicle. If the 9th Century recipe does lead to new drugs, they might be useful against MRSA skin infections such as those that cause foot ulcers in people with diabetes. These are usually antibiotic-resistant
Antibiotics are generally synthesized in nature by bacteria (or other microbes) as defenses against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Almost all bacterial species cannot be grown in the lab using practical methods. That hasn’t changed for decades. But those bacteria grow fine in the environment, typically the soil. So… can we isolate antibiotics from the soil?
3 months earlier, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying. … “We are running out of options to save Tom. What do you think about phage therapy?”
An alarming number of bacteria are now resistant to one or more antibiotics, so this new line of inquiry would certainly be welcomed if it proves effective.
In their recent study, Dr. Edgell and his colleagues successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. By programming the Cas9 to view the bacterium itself as the enemy, Dr. Edgell and his colleagues were able to force Salmonella to make lethal cuts to its own genome.
As we discover more of the benefits of our microbiota, it would also be interesting to have a solution to bacterial infections which doesn’t create problems for our “good bacteria.
So overall, this is an impressive paper. The combination of what appears to be pretty rigorous ML work with actual assay data generated just for this project seems to have worked out well, and represents, I would say, the current state of the art. It is not the “Here’s your drug!” virtual screening of fond hopes and press releases, but it’s a real improvement on what’s come before and seems to have generated things that are well worth following up on. I would be very interested indeed in seeing such technology applied to other drug targets and other data sets – but then, that’s what people all around academia and industry are trying to do right now. Let’s hope that they’re doing it with the scope and the attention to detail presented in this work.
Researchers have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance. This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance
If something isn’t done now, antibiotic-resistant bacteria could kill as many as 10M people a year by 2050. A little-known Boston nonprofit could be our best hope.
This discovery underscores how important it is to include biofilms in any studies of antibacterial compounds because being able to kill planktonic cultures bears no relation to being able to break down biofilm.
2021-10-14: Another approach is to modify bacteria to destroy the MSRA biofilms
Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.
2023-05-23: Odd that phage therapy only made progress in former soviet republics
“Phages” are little known outside the former countries of the Soviet Union, which did the most to develop the idea. In Georgia they have been part of the local pharmacopoeia for decades. (Indeed, 2023 marks the Eliava’s centenary.) Little vials containing stale-tasting liquid full of anti-bacterial viruses can be bought at pharmacies across Tbilisi. Now, as worries about antibiotic resistance build, Western firms are taking a second look.
In a series of experiments on earthworms, scientists have identified PHA-4, which plays a critical role in prolonging life without tapping into insulin-regulating neural pathways that also control the aging process.
I bet they are partying over at SENS. 2007-08-13: The baby boomers don’t want to die, like all prior generations. but unlike them, they have the financial means to massively fund anti-aging research like SENS. This is only the very beginning. 2008-01-09: I wonder whether CR is compatible with evolutionary fitness. 2008-05-26: Intrinsic Pluripotency
We show that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells. The discovery has major implications for large scale production of specialized cells, such as brain, heart muscle and insulin producing cells, for future therapeutic use.
Prematurely aged (shortened) telomeres appears to be a common feature of iPS cells created by current pluripotency protocols. However, the spontaneous appearance of lines that express sufficient telomerase activity to extend telomere length may allow the reversal of developmental aging in human cells for use in regenerative medicine.
Injecting pluripotent cells into your blood stream can reverse aging effects. 2013-09-18: Google used to say, cheekily, that making search faster times billions of users saves lives, so doing anti aging seems like the logical next step. I also like this because it couldn’t be further from all the web 2.0 incrementalist nonsense most startups limit themselves to. 2014-06-13: Stem cell pills
I started taking Stem Cell 100 back in 2011. It is $60 for a 1 month supply. There is now Stem Cell 100+ [$75 for a 1 month supply]. They added more ingredients and the testimonials are that it acts faster and is more powerful and more people have noticeable positive changes.
Let’s face it – any other syndrome that caused the sorts of effects that age does on our bodies would be considered a plague. But we’re used to it, and it happens to everyone, and it happens slowly. Does it have to be that way? The history of medicine is a refusal to play the cards that we’ve been dealt, and there’s no reason to stop now.
the age of an organism, or an organ like the brain, is not written in stone. It is malleable. You can move it in 1 direction or the other. It’s almost mythological that something in young organisms can maintain youthfulness, and it’s probably true.
children of centenarians, who have a good chance of becoming centenarians themselves, maintained their telomeres at a “youthful” level corresponding to 60 years of age — even when they became 80 or older. Centenarian offspring also maintained lower levels of markers for chronic inflammation.
Almost any amount and type of physical activity may slow aging deep within our cells. And middle age may be a critical time to get the process rolling, at least by one common measure of cell aging.
Nearly 10 years of research showing that Rapamycin makes mice live up to 60% longer, scientists are trying it out as an anti-aging drug in dogs and humans. Researchers gave rapamycin to 16 dogs and imaged their hearts. “It started to function better. It started to look like a more youthful heart”. Those dogs took rapamycin for only 10 weeks.
The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. Treating mice with a NAD+ precursor, or “booster,” called NMN improved their cells’ ability to repair DNA damage caused by radiation exposure or old age. “The cells of the old mice were indistinguishable from the young mice, after just 1 week of treatment”. Human trials of NMN therapy will begin within 6 months. “This is the closest we are to a safe and effective anti-aging drug that’s perhaps only 3 to 5 years away from being on the market if the trials go well”
There is much to be optimistic about and the ideas proposed by SENS over 10 years ago and widely criticized are now being eagerly explored by researchers as it becomes ever more apparent that the aging processes are amenable to intervention. What was mocked just over 10 years ago is now becoming an accepted approach to treating age-related diseases as the result continue to mount up in support of a repair based approach to aging. However we still lack complete knowledge on several age-related damages to progress to clinical trials in humans.
Targeting multiple aging pathways has the potential to significantly reduce blood pressure and stress, while significantly increasing HDL Cholesterol levels and lung capacity. Targeting multiple critical aging pathways with a single dietary supplement is a novel alternative strategy to promote overall health.
“We have already done a bunch of trials in mice and we are doing some in dogs, and then we’ll move on to humans”. The US pet industry is a $72B-a-year market.
The prolongation of human lifespan is “the biggest thing that is going to happen in the 21st century. It’s going to make what Elon Musk is doing look fairly pedestrian.”
Rejuvenate Bio has met with investors and won a grant from the US Special Operations Command to look into “enhancement” of military dogs while Harvard is seeking a broad patent on genetic means of aging control in species including the “cow, pig, horse, cat, dog, rat, etc.”
The team hit on the idea of treating pets because proving that it’s possible to increase longevity in humans would take too long. “You don’t want to go to the FDA and say we extend life by 20 years. They’d say, ‘Great, come back in 20 years with the data’”.
Aubrey De Grey discusses how all of the aspects of fighting the damage of aging have reached an investable stage. 10 years ago only stem cells were investable. Now companies have been formed to attempt to counter all of the types of aging damage.
George Church talks about reversing human aging and claims they made mice live 2x as long. Organ longevity has also been done successfully with entire mice. If the body still did not get rid of the substandard cells then work at Oisin Biotechnology and others would enable bad cells to be cleared. Oisin is extending the life of mice and has proven safety and improvement in monkeys. They will start human clinical trials in 2019. Rejuvenate Bio has 60 aging reversal gene therapies. They have mentioned but not yet published eye popping results in mice. They are testing aging reversal in dogs in 2018-2019. Human treatments could be available on a general basis by 2025.
There is increasing of pharmaceutical company engagement via disease-focused proof of concept trials. Curing all cancers would add 3.5 years to average human lifespan. If anti-aging could delay the start of aging disease from 50 or 60 by 20 or 30 years then this could be 10x better than curing cancer. $50b per year is spent on curing cancer. If medical research was allocated based upon potential impact then anti-aging should be at a funding level of $500 billion per year.
His anti aging regimen is to activate pathways to improve the body’s defenses against aging. He is testing NMN on human subjects. He describes NMN is fuel for sirtuins. NMN is related to NR. NR increases the levels of NAD. Sirtuins need NAD to work. We lose NAD as we age. We have half of the NAD by the time we are 50. He takes a gram of NMN (Nicotinamide MonoNucleotide) and takes half a gram resveratrol in the morning with yogurt. He is personally taking 1 gram of Metformin once a day at night.
the evidence as it stands weakly supports the conclusion that CR modestly extends human life. We expect that an individual engaging in 20-30% CR versus a normative, non-obesogenic diet without malnutrition might enjoy a 10%-20% increase in longevity. A 10%-15% CR relative to a normative diet may increase lifespan by perhaps 5-10%.
The treated cells appeared to be ~3 years younger on average than untreated cells from elderly people, with peaks of 3 years (in skin cells) and 7 years (in cells that line blood vessels).
Sinclair’s focus in on analog information loss, the epigenetic noise that accumulates in the methylation patterns running along our DNA and disturbing its expression. This degradation is a biological clock of aging, and today’s results “tell us the clock doesn’t just represent time—it is time. If you wind the hands of the clock back, time also goes backward.”
“Harvard Medical School scientists have successfully restored vision in mice by turning back the clock on aged eye cells in the retina to recapture youthful gene function. The achievement represents the first successful attempt to reverse glaucoma-induced vision loss, rather than merely stem its progression
2020-12-04: Most brain aging decline can be fixed overnight
Common signs of neuronal aging disappeared literally overnight: neurons’ electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.
Avian longevity may be linked to special adaptations in the biology of birds—including proteins to operate their highly efficient metabolisms and their remarkable ways of processing oxygen—that prevent tissue damage commonly associated with old age. In many animals, high body temperature, metabolic rates, and blood glucose levels indicate a shorter lifespan because these systems damage DNA in the mitochondria. But compared to other animals, birds are very good at protecting their mitochondrial DNA from the cellular damage associated with aging, which could contribute to their extensive lifespans. Studying birds could enhance our understanding of aging in humans, too, leading to advances in human health. “We want to know how nature has constructed things that resist aging better than we do. Otherwise, we’re left to our own ingenuity.”
2023-01-29: Epigenetic clocks have become more accurate and more universal
“A pan-tissue clock was paradoxical because methylation is supposed to control cell identity,” and remains fixed through adulthood. When Horvath and his colleagues established that epigenetic clocks counted time at the same pace across all tissues, whether that was quickly dividing blood cells or notoriously slow and highly differentiated brain neurons, the race was on to understand the fabric of time that the clocks are measuring. The universal clock, the key finding of Horvath’s 2022 paper, takes the pan-tissue clock one step further. It chimed the final stroke that unequivocally showed a predictable pattern to aging not only within the body of a single organism, but across mammals. These are clocks that hopefully are comprised of cytosines that truly have a causative role in the aging process. Of particular interest are “enhancer” regions of the genome, which exaggerate the role of certain genes by activating them to exorbitant levels.
The commitment made yesterday by rich countries to buy a suitable vaccine, meeting internationally recognized standards for efficacy and safety, could transform the economics of development of new vaccines. Pause briefly on how radical this policy is. There is a social need for extra R&D and investment in production facilities. But instead of paying researchers to do that research – which might or might not succeed, they are creating market incentives and allowing competition to do the rest. The donors create a reward for the private sector – the prospect of a lucrative market for vaccines – which enables firms to invest in developing and producing the needed vaccines. But if the research fails it will cost the donors nothing. The taxpayer will only have to cough up if the vaccines are actually developed and used. And if the vaccine is used, it will save more than 5m lives over the next 25 years – at $300 per life saved, a bargain in development terms. For firms, this is attractive because it creates a whole new market for their products, and enables them to serve poor country markets on a commercial basis, rather than as an act of corporate social responsibility. And for developing countries, they have the prospect of access to new vaccines, which in the past have taken 15-20 years to be mass produced cheaply enough for them to be widely used in developing countries. So this is an results-based, market-oriented, hard-headed partnership between donors, developing countries and the pharmaceutical industry which, if it works, will solve one of the most important health challenges on the planet.
Unbeknownst to Glickman, the clubfooted man had spiked his drink with LSD. The aftereffects of the acid trip sent him into a lifelong tailspin of psychosis, electroshock therapy, and terrifying hallucinations. He had no idea what had happened to him—this was 1952, at least 10 years before most people had even heard of the drug.
Gregor J. Rothfuss 