courtesy of Freepik
For 100 years, calorie restriction has been one of the few proven ways to significantly prolong lifespan: sometimes at the expense of precious muscle mass, connection, and quality of life. But rapamycin, a drug discovered in the soils of mysterious Easter Island, might offer the same longevity benefits as eating fewer calories–sans a rumbling tummy.
Fasting without fasting
A new study published in Aging Cell suggests that rapamycin, an immunosuppressant drug with rising longevity hype, offers similar lifespan benefits to fasting in various animals. This could offer huge promise for aging adults at increased risk of muscle loss and age-related disease. 💪🧠
But life extension benefits in mice, killifish, and dogs can only tell us so much about how it would affect people…so here’s what we know so far.
🌱 Your Daily Dose of Youthful Aging
Sponsored Content by NativePath
Ah, collagen–the nutrient responsible for skin elasticity, joint mobility, and gut health. Unfortunately, your body’s ability to produce collagen drops in your 30s, and not all collagen is created equal.
Read more here
How it works
🪺 First discovered in the 1970s in soil bacteria on Easter Island, rapamycin (derived from the Rapanui plant) showed impressive immunosuppressive and antibiotic properties, making it useful for organ transplant patients.
In 2009, a landmark study proved it has longevity benefits in mice, launching its popularity and “creating a sea-change in how researchers viewed aging.”
Rapamycin inhibits activity in the mTOR (mechanistic target of rapamycin) pathway–calorie restriction affects the same one.
⚙️ mTOR fundamentally tells cells when to build proteins, use energy, and clean house. It’s the “master regulator of cell growth,” controlling processes responsible for cells growing and dividing.
🧬 This is critical for our young and developing bodies and brains. But mTOR becomes TOO ACTIVE as we age; this is significantly linked to physiological aging and disease, risk factors for diabetes, heart disease, dementia, and cancer.
mTOR is also just a fundamental driver of aging and mortality. 📉 Even a slight increase in mTOR activity can shorten lifespan by 20% (16 human years) in animals, according to Nature Aging via News Medical.
Rapamycin vs. calorie restriction
In a massive meta-analysis of 167 studies across eight vertebrate species, researchers compared how two proposed diet-mimicking drugs–rapamycin and metformin–and dietary restriction (fasting or calorie reduction) influenced lifespan.
🥇 Eating less was the winner, but rapamycin was nearly as effective for lifespan and acts on the same biological pathways. These longevity benefits were present in both males and females.
→This checks out. Fasting is a tried and true method to extend lifespan in many species.
This 1980s study shows a 30% increase in lifespan in mice when calories were dramatically reduced.
🧹 Fasting triggers autophagy, a cellular ‘recycling system’ that helps us get rid of proteins and molecular debris that can become toxic and cause disease. Autophagy turns on when mTOR is suppressed.
⚠️ Interestingly, metformin offered no clear benefits to life extension. Although it may promote ‘exceptional longevity’ in post-menopausal women with type two diabetes, metformin has not really been studied in healthy adults.
So why not just eat less?
Calorie restriction can be a hard sell—chronic hunger, social isolation, muscle loss, and diminished quality of life are possible downsides. 🚫 And even if it works in mice (or killifish or dogs or worms…) it does not mean it’s scaleable to humans, or offers the same benefits.
Photo by Perry Fel on Unsplash
“You always have to be careful when you’re looking across different species,” says Matt Kaeberlein, a University of Washington researcher and founder of the dog aging project, in a conversation with New Scientist. 🔬 The shorter an organism’s lifespan, the more likely the effects are going to be bigger.
💪 The Muscle Tradeoff: In a 2024 study done in mice, 40% calorie restriction produced the greatest lifespan benefits and slowed aging…at the cost of lean muscle mass loss, compromised immune function, and lower resilience. This could present deleterious effects in real-world situations.
You need muscle for strength, stamina, and daily activities. It is also metabolically useful—muscle burns more calories than fat. This can support immune health, cognition, energy. It also supports healthy weight maintenance, which can prevent cardiovascular disease, stroke, and protect healthspan.
Longevity isn’t guesswork. It’s data
Sponsored Content by Wild Health
We all want to live longer—but more importantly, we want to feel good while we do it. Wild Health blends genomics, advanced diagnostics, and concierge care to build your personalized plan for better energy, resilience, and long-term health. This isn’t more to-dos. It’s a smarter way to care for yourself.
Learn How It Works
Real-world potential
courtesy of Freepik
Off-label use ‘hints’ at treating age-related diseases, Kaeberlein says. This includes:
🧠 Alzheimer’s
🦠Autoimmune diseases
🩸 Metabolic and cardiovascular disease
💥 Chronic Fatigue Syndrome
🧬 Even some cancers
Rapamycin appears to boost blood flow and preserve brain volume in people with a high risk of dementia. Kaeberlein’s lab is studying rapamycin in dogs too, and he’s optimistic.
“I never thought rapamycin would be the popular topic in longevity,” Kaeberlein said in an exclusive interview with Club Livelong. Yet here we are.
But there are side effects to consider. The most common? Canker sores. 🛡️ Rapamycin can also weaken the immune system—which is already more vulnerable in older adults—and slow reproduction, wound healing, and affect kidneys.
According to study author Zahida Sultanova of the University of East Anglia, UK, rapalogs offer a promising alternative with fewer side effects, writes New Scientist.
Still, there’s so much we just don’t know…does it even work in people?
“It’s really frustrating” Kaeberlein tells Livelong. “We still haven't had the definitive clinical trials. They should have been done 15 years ago. They should be done today…They're not happening.”
💡 Key Takeaway
For adults who find fasting or calorie-cutting unsustainable, rapamycin could be an exciting alternative with other benefits. But experts don’t recommend it for anti-aging or lifespan—the human evidence just isn’t there.
The challenge ahead, as Sultanova puts it, is to “produce therapies that make us healthier for longer without compromising our quality of life – or our taste for the occasional slice of chocolate cake.” 🍫🎂
Poll
❓Last week’s chilly question: Which ‘extreme’ longevity practice would you rather commit to?
→ 🧊 Cold plunge, 🔥 sauna, 🧘♂️ fast, or ✨ something else?
Cold plunge wins (37%)! Fasting takes second, followed by sauna and something else entirely. Surprising, since fasting gets the most research and press.
Reply and tell us: Why do you cold plunge?
Over 70% of us say we’ve heard conflicting information about vitamins and supplements. So… what actually works? Dr. Tod Cooperman, founder of ConsumerLab.com, cuts through the confusion and shares what’s worth your money—and what isn’t.
→ Register here
Until next time,
The information provided about wellness and health is for general informational and educational purposes only. We are not licensed medical professionals, and the content here should not be considered medical advice. Talk to a doctor before trying any of these suggestions.
Longevity Media LLC
Look good, feel better, live longer.