Rapamycin Can Slow Aging By 20% (But Watch Out)
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Rapamycin’s Pros & Cons
Rapamycin is generally heralded as a wonderdrug that (according to best evidence so far) can slow down aging, potentially adding decades to human lifespan—and yes, healthspan.
It comes from a kind of soil bacteria, which in turn comes from the island of Rapa Nui (a Chilean territory best known for its monumental moai statues), hence the name rapamycin.
Does it work?
Yes! Probably! With catches!
Like most drugs that are tested for longevity-inducing properties, research in humans is very slow. Of course for drugs in general, they must go through in vitro and in vivo animal testing first before they can progress to human randomized clinical trials, but for longevity-inducing drugs, it’s tricky to even test in humans, without waiting entire human lifetimes for the results.
Nevertheless, mouse studies are promising:
Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
(“Easter Island” is another name given to the island of Rapa Nui)
That’s not a keysmash in the middle there, it’s a reference to rapamycin’s inhibitory effect on the kinase mechanistic target of rapamycin, sometimes called the mammalian target of rapamycin, and either way generally abbreviated to “mTOR”—also known as “FK506-binding protein 12-rapamycin-associated protein 1” or “FRAP1“ to its friends, but we’re going to stick with “mTOR”.
What’s relevant about this is that mTOR regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription.
Don’t those words usually get associated with cancer?
They do indeed! Rapamycin and its analogs have well-demonstrated anti-cancer potential:
❝Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo.
Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer.❞
…and as such, gets used sometimes as an anticancer drug—especially against renal cancer. See also:
Research perspective: Cancer prevention with rapamycin
What’s the catch?
Aside from the fact that its longevity-inducing effects are not yet proven in humans, the mouse models find its longevity effects to be sex-specific, extending the life of male mice but not female ones:
Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects
One hypothesis about this is that it may have at least partially to do with rapamycin’s immunomodulatory effect, bearing in mind that estrogen is immune-enhancing and testosterone is immunosuppressant.
And rapamycin? That’s another catch: it is an immunosuppressant.
This goes in rapamycin’s favor for its use to avoiding rejection when it comes to some transplants (most notably including for kidneys), though the very same immunosuppressant effect is a reason it is contraindicated for certain other transplants (such as in liver or lung transplants), where it can lead to an unacceptable increase in risk of lymphoma and other malignancies:
Prescribing Information: Rapamune, Sirolimus Solution / Sirolimus Tablet
(Sirolimus is another name for rapamycin, and Rapamune is a brand name)
What does this mean for the future?
Researchers think that rapamycin may be able to extend human lifespan to a more comfortable 120–125 years, but acknowledge there’s quite a jump to get there from the current mouse studies, and given the current drawbacks of sex-specificity and immunosuppression:
Advances in anti-aging: Rapamycin shows potential to extend lifespan and improve health
Noteworthily, rapamycin has also shown promise in simultaneously staving off certain diseases associated most strongly with aging, including Alzheimer’s and cardiac disease—or even, starting earlier, to delay menopause, in turn kicking back everything else that has an uptick in risk peri- or post-menopause:
Effect of Rapamycin in Ovarian Aging (Rapamycin)
👆 an upcoming study whose results are thus not yet published, but this is to give an idea of where research is currently at. See also:
Pilot Study Evaluates Weekly Pill to Slow Ovarian Aging, Delay Menopause
Where can I try it?
Not from Amazon, that’s for sure!
It’s still tightly regulated, but you can speak with your physician, especially if you are at risk of cancer, especially if kidney cancer, about potentially being prescribed it as a preventative—they will be able to advise about safety and applicability in your personal case.
Alternatively, you can try getting your name on the list for upcoming studies, like the one above. ClinicalTrials.gov is a great place to watch out for those.
Meanwhile, take care!
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Woman Petitions Health Insurer After Company Approves — Then Rejects — Her Infusions
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When KFF Health News published an article in August about the “prior authorization hell” Sally Nix said she went through to secure approval from her insurance company for the expensive monthly infusions she needs, we thought her story had a happy ending.
That’s because, after KFF Health News sent questions to Nix’s insurance company, Blue Cross Blue Shield of Illinois, it retroactively approved $36,000 worth of treatments she thought she owed. Even better, she also learned she would qualify for the infusions moving forward.
Good news all around — except it didn’t last for long. After all, this is the U.S. health care system, where even patients with good insurance aren’t guaranteed affordable care.
To recap: For more than a decade, Nix, of Statesville, North Carolina, has suffered from autoimmune diseases, chronic pain, and fatigue, as well as a condition called trigeminal neuralgia, which is marked by bouts of electric shock-like pain that’s so intense it’s commonly known as the “suicide disease.”
“It is a pain that sends me to my knees,” Nix said in October. “My entire family’s life is controlled by the betrayal of my body. We haven’t lived normally in 10 years.”
Late in 2022, Nix started receiving intravenous immunoglobulin infusions to treat her diseases. She started walking two miles a day with her service dog. She could picture herself celebrating, free from pain, at her daughter’s summer 2024 wedding.
“I was so hopeful,” she said.
But a few months after starting those infusions, she found out that her insurance company wouldn’t cover their cost anymore. That’s when she started “raising Cain about it” on Instagram and Facebook.
You probably know someone like Sally Nix — someone with a chronic or life-threatening illness whose doctor says they need a drug, procedure, or scan, and whose insurance company has replied: No.
Prior authorization was conceived decades ago to rein in health care costs by eliminating duplicative and ineffective treatment. Not only does overtreatment waste billions of dollars every year, but doctors acknowledge it also potentially harms patients.
However, critics worry that prior authorization has now become a way for health insurance companies to save money, sometimes at the expense of patients’ lives. KFF Health News has heard from hundreds of people in the past year relating their prior authorization horror stories.
When we first met Nix, she was battling her insurance company to regain authorization for her infusions. She’d been forced to pause her treatments, unable to afford $13,000 out-of-pocket for each infusion.
Finally, it seemed like months of her hard work had paid off. In July, Nix was told by staff at both her doctor’s office and her hospital that Blue Cross Blue Shield of Illinois would allow her to restart treatment. Her balance was marked “paid” and disappeared from the insurer’s online portal.
But the day after the KFF Health News story was published, Nix said, she learned the message had changed. After restarting treatment, she received a letter from the insurer saying her diagnoses didn’t actually qualify her for the infusions. It felt like health insurance whiplash.
“They’re robbing me of my life,” she said. “They’re robbing me of so much, all because of profit.”
Dave Van de Walle, a spokesperson for Blue Cross Blue Shield of Illinois, said the company would not discuss individual patients’ cases.
“Prior authorization is often a requirement for certain treatments,” Van de Walle said in a written statement, “and BCBSIL administers benefits according to medical policy and the employer’s benefit.”
But Nix is a Southern woman of the “Steel Magnolia” variety. In other words, she’s not going down without a fight.
In September, she called out her insurance company’s tactics in a http://change.org/ campaign that has garnered more than 21,000 signatures. She has also filed complaints against her insurance company with the U.S. Department of Health and Human Services, U.S. Department of Labor, Illinois Department of Insurance, and Illinois attorney general.
Even so, Nix said, she feels defeated.
Not only is she still waiting for prior authorization to restart her immunoglobulin infusions, but her insurance company recently required Nix to secure preapproval for another treatment — routine numbing injections she has received for nearly 10 years to treat the nerve pain caused by trigeminal neuralgia.
“It is reprehensible what they’re doing. But they’re not only doing it to me,” said Nix, who is now reluctantly taking prescription opioids to ease her pain. “They’re doing it to other patients. And it’s got to stop.”
Do you have an experience with prior authorization you’d like to share? Click here to tell your story.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
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Capsaicin For Weight Loss And Against Inflammation
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Capsaicin’s Hot Benefits
Capsaicin, the compound in hot peppers that makes them spicy, is a chemical irritant and a neurotoxin. However, humans being humans, we decided to eat them for fun.
In contrast to many other ways in which humans recreationally enjoy things that are objectively poisonous, consuming capsaicin (in moderation) is considered to have health benefits, such as aiding weight loss (by boosting metabolism) and reducing inflammation.
Let’s see what the science says…
First: is it safe?
Capsaicin is classified as “Generally Recognized As Safe”. That said, the same mechanism that causes them to boost metabolism, does increase blood pressure:
Mechanisms underlying the hypertensive response induced by capsaicin
If you are in good cardiovascular health, this increase should be slight and not pose any threat, unless for example you enter a chili-eating contest when not acclimated to such:
Capsaicin and arterial hypertensive crisis
As ever, if unsure, do check with your doctor first, especially if you are taking any blood pressure medications, or otherwise have known blood pressure issues.
Does it really boost metabolism?
It certainly does; it works by increasing oxygen consumption and raising body temperature, both of which mean more calories will be burned for the same amount of work:
Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications
This means, of course, that chili peppers enjoy the status of being functionally a “negative calorie” food, and a top-tier one at that:
Chili pepper as a body weight-loss food
Here’s a good quality study that showed a statistically significant* fat loss improvement over placebo:
*To put it in numbers, the benefit was:
- 5.91 percentage points lower body fat percentage than placebo
- 6.68 percentage points greater change in body fat mass than placebo
See also: Difference between percentages and percentage points
For those who prefer big reviews than single studies, we’ve got you covered:
Does it really reduce inflammation?
Counterintuitive as it may seem, yes. By means of reducing oxidative stress. Given that things that reduce oxidative stress tend to reduce inflammation, and in turn tend to reduce assorted disease risks (from diabetes to cancer to Alzheimer’s), this probably has more knock-on benefits too, but we don’t have room to explore all of those today.
Fresh peppers are best for this, but dried peppers (such as when purchased as a ground spice in the supermarket, or when purchased as a capsule-based supplement) still have a very respectable anti-inflammatory effect:
- Capsaicinoids, Polyphenols and Antioxidant Activities of Capsicum annuum: Comparative Study of the Effect of Ripening Stage and Cooking Methods
- A Review on the Effect of Drying on Antioxidant Potential of Fruits and Vegetables
How much should we take?
It’s recommended to start at a low dose and gradually increase it, but 2–6mg of capsaicin per day is the standard range used in studies.
If you’re getting this from peppers, then for example cayenne pepper (a good source of capsaicin) contains around 2.5mg of capsaicin per 1 gram of cayenne.
In the case of capsules, if for example you don’t like eating hot pepper, this will usually mean taking 2–6 capsules per day, depending on dosage.
Make sure to take it with plenty of water!
Where can we get it?
Fresh peppers or ground spice from your local grocery store is fine. Your local health food store probably sells the supplements, too.
If you’d like to buy it online, here is an example product on Amazon.
Note: options on Amazon were more limited than usual, so this product is not vegan, and probably not halal or kosher, as the capsule contains an unspecified gelatin.
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Younger – by Dr. Sara Gottfried
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Does this do the things it says in the subtitle? In honestly, not really, no, but what it does do (if implemented) is modify your gene expression, slow aging, and extend healthspan. Which is all good stuff, even if it’s not the snappy SEO-oriented keywords in the subtitle.
A lot of the book pertains to turning certain genes (e.g. SIRT1, mTOR, VDR, APOE4, etc) on or off per what is sensible in each case, noting that while genes are relatively fixed (technically they can be changed, but the science is young and we can’t do much yet), gene expression is something we can control quite a bit. And while it may be unsettling to have the loaded gun that is the APOE4 gene being held against your head, at the end of the day there are things we can do that influence whether the trigger gets pulled, and when. Same goes for other undesirable genes, and also for the desirable ones that are useless if they never actually get expressed.
She offers (contained within the book, not as an upsell) a 7-week program that aims to set the reader up with good healthy habits to do just that and thus help keep age-related maladies at bay, and if we slip up, perhaps later in the year or so, we can always recommence the program.
The advice is also just good health advice, even without taking gene expression into account, because there are a stack of benefits to each of the things in her protocol.
The style is personable without being padded with fluff, accessible without dumbing down, and information-dense without being a challenging read. The formatting helps a lot also; a clear instructional layout is a lot better than a wall of text.
Bottom line: if you’d like to tweak your genes for healthy longevity, this book can help you do just that!
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Men have a biological clock too. Here’s what’s more likely when dads are over 50
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We hear a lot about women’s biological clock and how age affects the chance of pregnancy.
New research shows men’s fertility is also affected by age. When dads are over 50, the risk of pregnancy complications increases.
Data from more than 46 million births in the United States between 2011 and 2022 compared fathers in their 30s with fathers in their 50s.
While taking into account the age of the mother and other factors known to affect pregnancy outcomes, the researchers found every ten-year increase in paternal age was linked to more complications.
The researchers found that compared to couples where the father was aged 30–39, for couples where the dad was in his 50s, there was a:
- 16% increased risk of preterm birth
- 14% increased risk of low birth weight
- 13% increase in gestational diabetes.
The older fathers were also twice as likely to have used assisted reproductive technology, including IVF, to conceive than their younger counterparts.
Steven van Loy/Unsplash Dads are getting older
In this US study, the mean age of all fathers increased from 30.8 years in 2011 to 32.1 years in 2022.
In that same period, the proportion of men aged 50 years or older fathering a child increased from 1.1% to 1.3%.
We don’t know the proportion of men over 50 years who father children in Australia, but data shows the average age of fathers has increased.
In 1975 the median age of Australian dads was 28.6 years. This jumped to 33.7 years in 2022.
How male age affects getting pregnant
As we know from media reports of celebrity dads, men produce sperm from puberty throughout life and can father children well into old age.
However, there is a noticeable decline in sperm quality from about age 40.
Female partners of older men take longer to achieve pregnancy than those with younger partners.
A study of the effect of male age on time to pregnancy showed women with male partners aged 45 or older were almost five times more likely to take more than a year to conceive compared to those with partners aged 25 or under. More than three quarters (76.8%) of men under the age of 25 years impregnated their female partners within six months, compared with just over half (52.9%) of men over the age of 45.
Pooled data from ten studies showed that partners of older men are also more likely to experience miscarriage. Compared to couples where the male was aged 25 to 29 years, paternal age over 45 years increased the risk of miscarriage by 43%.
Older men are more likely to need IVF
Outcomes of assisted reproductive technology, such as IVF, are also influenced by the age of the male partner.
A review of studies in couples using assisted reproductive technologies found paternal age under 40 years reduced the risk of miscarriage by about 25% compared to couples with men aged over 40.
Having a male under 40 years also almost doubled the chance of a live birth per treatment cycle. With a man over 40, 17.6% of treatment rounds resulted in a live birth, compared to 28.4% when the male was under 40.
How does male age affect the health outcomes of children?
As a result of age-related changes in sperm DNA, the children of older fathers have increased risk of a number of conditions. Autism, schizophrenia, bipolar disorders and leukaemia have been linked to the father’s advanced years.
A review of studies assessing the impact of advanced paternal age reported that children of older fathers have increased rates of psychiatric disease and behavioural impairments.
But while the increased risk of adverse health outcomes linked to older paternal age is real, the magnitude of the effect is modest. It’s important to remember that an increase in a very small risk is still a small risk and most children of older fathers are born healthy and develop well.
Improving your health can improve your fertility
In addition to the effects of older age, some chronic conditions that affect fertility and reproductive outcomes become more common as men get older. They include obesity and diabetes which affect sperm quality by lowering testosterone levels.
While we can’t change our age, some lifestyle factors that increase the risk of pregnancy complications and reduce fertility, can be tackled. They include:
- smoking
- recreational drug taking
- anabolic steroid use
- heavy alcohol consumption.
Get the facts about the male biological clock
Research shows men want children as much as women do. And most men want at least two children.
Yet most men lack knowledge about the limitations of female and male fertility and overestimate the chance of getting pregnant, with and without assisted reproductive technologies.
We need better public education, starting at school, to improve awareness of the impact of male and female age on reproductive outcomes and help people have healthy babies.
For men wanting to improve their chance of conceiving, the government-funded sites Healthy Male and Your Fertility are a good place to start. These offer evidence-based and accessible information about reproductive health, and tips to improve your reproductive health and give your children the best start in life.
Karin Hammarberg, Senior Research Fellow, Global and Women’s Health, School of Public Health & Preventive Medicine, Monash University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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How To Keep Your Mind From Wandering
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Whether your mind keeps wandering more as you get older, or you’re a young student whose super-active brain is more suited to TikTok than your assigned reading, sustained singular focus can be a challenge for everyone—and yet (alas!) it remains a required skill for so much in life.
Today’s edition of 10Almonds presents a nifty trick to get yourself through those tasks! We’ll also be taking some time to reply to your questions and comments, in our weekly interactive Q&A.
First of all though, we’ve a promise to make good on, so…
How To Stay On The Ball (Or The Tomato?) The Easy Way
For most of us, we face three main problems when it comes to tackling our to-dos:
- Where to start?
- The task seems intimidating in its size
- We get distracted and/or run out of energy
If you’re really not sure where to start, we recommended a powerful tool in last Friday’s newsletter!
For the rest, we love the Pomodoro Technique:
- Set a timer for 25 minutes, and begin your task.
- Keep going until the timer is done! No other tasks, just focus.
- Take a 5-minute break.
- Repeat
This approach has three clear benefits:
- No matter the size of the task, you are only committing to 25 minutes—everything is much less overwhelming when there’s an end in sight!
- Being only 25 minutes means we are much more likely to stay on track; it’s easier to defer other activities if we know that there will be a 5-minute break for that soon.
- Even without other tasks to distract us, it can be difficult to sustain attention for long periods; making it only 25 minutes at a time allows us to approach it with a (relatively!) fresh mind.
Have you heard that a human brain can sustain attention for only about 40 minutes before focus starts to decline rapidly?
While that’s been a popular rationale for school classroom lesson durations (and perhaps coincidentally ties in with Zoom’s 40-minute limit for free meetings), the truth is that focus starts dropping immediately, to the point that one-minute attention tests are considered sufficient to measure the ability to focus.
So a 25-minute Pomodoro is a more than fair compromise!
Why’s it called the “Pomodoro” technique?
And why is the 25-minute timed work period called a Pomodoro?
It’s because back in the 80s, university student Francesco Cirillo was struggling to focus and made a deal with himself to focus just for a short burst at a time—and he used a (now “retro” style) kitchen timer in the shape of a tomato, or “pomodoro”, in Italian.
If you don’t have a penchant for kitsch kitchenware, you can use this free, simple Online Pomodoro Timer!
(no registration/login/download necessary; it’s all right there on the web page)
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Avocado, Coconut & Lime Crumble Pots
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This one’s a refreshing snack or dessert, whose ingredients come together to make a very good essential fatty acid supplement. Coconut is a good source of MCTs, avocados are rich in omega 3, 6, and 9, while chia seeds are a great ALA omega 3 food, topping up the healthy balance.
You will need
- flesh of 2 large ripe avocados
- grated zest and juice of 2 limes
- 3 tbsp coconut oil
- 1 tbsp chia seeds
- 2 tsp honey (omit if you prefer a less sweet dish)
- 1 tsp desiccated coconut
- 4 low-sugar oat biscuits
Method
(we suggest you read everything at least once before doing anything)
1) Blend the avocado, lime juice, coconut oil, honey, and half the desiccated coconut, in a food processor.
2) Scoop the mixture into 4 ramekins (or equivalent-sized glasses), making sure to leave a ½” gap at the top. Refrigerate for at least 2–4 hours (longer is fine if you’re not ready to serve yet).
3) Assemble, by crumbling the oat biscuits and sprinkling on top of each serving, along with the other half of the desiccated coconut, the lime zest, and the chia seeds.
4) Serve immediately:
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
Take care!
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