#senolytics

[didanawisgi]

My Turn: Unlocking the senolytics puzzle

In the back of the telomere lab cell-culture room, in the oldest incubator, I had a pet dish of senescent cells for years.I was never able to teach them any tricks (well, they would stain blue for P16, but they can only do that trick once), but they...

[neurosciencenews]

It Is Possible to Reverse Damage Caused by Aging

A types of small molecules called senolytics can reverse the impact of aged, senescent cells.

The research is in Nature Medicine. (full access paywall)

[principleofplenitude]

Just by removing senescent cells, you could stimulate new tissue production,” says Jennifer Elisseeff, senior author of the cartilage paper and a biomedical engineer at Johns Hopkins University in Baltimore, Maryland. It jump-starts some of the tissue's natural repair mechanisms, she says. This anti-ageing phenomenon has been an unexpected twist in the study of senescent cells, a common, non-dividing cell type first described more than five decades ago. When a cell enters senescence — and almost all cells have the potential to do so — it stops producing copies of itself, begins to belch out hundreds of proteins, and cranks up anti-death pathways full blast. A senescent cell is in its twilight: not quite dead, but not dividing as it did at its peak. Now biotechnology and pharmaceutical companies are keen to test drugs — known as senolytics — that kill senescent cells in the hope of rolling back, or at least forestalling, the ravages of age. Unity Biotechnology in San Francisco, California, co-founded by van Deursen, plans to conduct multiple clinical trials over the next two-and-a-half years, treating people with osteoarthritis, eye diseases and pulmonary diseases. At Mayo, gerontologist James Kirkland, who took part in the 2011 study, is cautiously beginning a handful of small, proof-of-concept trials that pit senolytic drugs against a range of age-related ailments. “I lose sleep at night because these things always look good in mice or rats, but when you get to people you hit a brick wall,” says Kirkland.

“To stay young, kill zombie cells” from Nature

[thelovebudllc]

Master Senolytics and Hormetic Stress for Vitalit

How it works: Caloric restriction triggers autophagy and apoptosis, potentially clearing senescent cells. FMD mimics fasting with a low-calorie, plant-based diet. Our 5-Day Perfect Cleanse is based on this idea. Evidence: Researchers found that serum from calorie-restricted animals was able to delay senescence of normal human fibroblasts in vitro and significantly increase their lifespan in…

[thelovebudllc]

Senolytics offer hope for more precise Alzheimer's treatments

A new research paper was published in Aging (Aging-US) on March 29, 2025, as the cover of Volume 17, Issue 3, titled “Differential senolytic inhibition of normal versus Aβ-associated cholinesterases: implications in aging and Alzheimer’s disease.” In this study, a research team from Dalhousie University, led by Sultan Darvesh, discovered that certain anti-aging compounds, known as senolytics, can…

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[manywhelps-handleit]

The Fountain of Youth: The Fascinating Quest to Stay Younger with Rapamycin

Introduction:

Aging is an inevitable biological process that affects all living organisms, including humans. Throughout history, humanity has been on an eternal quest for the elusive fountain of youth, seeking ways to delay the effects of aging and extend lifespan. In recent years, there has been growing interest in rapamycin, a drug originally developed as an immunosuppressant, for its potential to slow down the aging process and enhance longevity. This article explores the scientific basis, mechanisms, and the burgeoning interest in rapamycin as a promising anti-aging intervention.

I. Unveiling the Science Behind Aging:

Aging is a complex and multifactorial process involving cellular, molecular, and genetic changes. Over time, cells undergo damage, telomeres shorten, and various regulatory pathways become less efficient. This gradual decline leads to age-related diseases such as cancer, neurodegeneration, cardiovascular disorders, and metabolic syndromes. Scientists have long sought to understand the fundamental mechanisms behind aging, leading to the emergence of the field of anti-aging research.

II. Rapamycin's Role in Aging:

Rapamycin, also known as sirolimus, is a macrolide compound first discovered in the soil of Easter Island (Rapa Nui) in the 1970s. Initially utilized as an immunosuppressant to prevent organ transplant rejection, researchers soon noticed its potential beyond immunosuppression. Studies in the early 2000s demonstrated that rapamycin could extend the lifespan of various model organisms, including yeast, worms, flies, and mice. This exciting discovery sparked widespread interest in rapamycin as an anti-aging agent.

III. Targeting the mTOR Pathway:

Rapamycin's anti-aging effects are primarily attributed to its inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway. mTOR is a master regulator that plays a central role in cell growth, proliferation, and metabolism. By inhibiting mTOR, rapamycin affects numerous cellular processes, including protein synthesis, autophagy, and mitochondrial function. These changes collectively contribute to the attenuation of age-related decline.

IV. Promising Results in Model Organisms:

Studies in various model organisms have provided compelling evidence for rapamycin's potential as an anti-aging intervention. In mice, rapamycin administration has been shown to extend lifespan and improve healthspan, delaying the onset of age-related diseases. Additionally, rapamycin has demonstrated positive effects on age-related cognitive decline and cardiac function in animal models. These findings have ignited hope for its translation to human application.

V. Human Trials and Challenges:

While rapamycin has shown remarkable anti-aging effects in animal studies, translating these findings to human trials presents significant challenges. The drug's immunosuppressive properties, though beneficial in organ transplantation, may pose risks and side effects when used long-term for anti-aging purposes. Dosing and timing also remain important considerations, as excessive or prolonged rapamycin use could lead to adverse effects on cellular function and immunity.

VI. Potential Benefits Beyond Aging:

Beyond its anti-aging potential, rapamycin has been investigated for its therapeutic benefits in various age-related diseases. Research suggests that rapamycin could be effective in treating certain types of cancer, Alzheimer's disease, and metabolic disorders such as type 2 diabetes. These additional benefits further highlight the drug's potential in promoting healthy aging and extending the human healthspan.

VII. Ethical and Societal Implications:

The pursuit of longevity and anti-aging interventions raises ethical and societal questions. Should access to anti-aging therapies be limited, considering potential disparities in health and longevity among different socioeconomic groups? Additionally, the quest to prolong life raises philosophical questions about the value of aging, the natural course of life, and the potential consequences of extending the human lifespan.

VIII. Future Directions:

As research into rapamycin and anti-aging continues, scientists are exploring alternative strategies and compounds that target similar pathways. Caloric restriction mimetics, such as metformin, have shown promise in preclinical studies. Gene therapies and senolytics, which target senescent cells, also hold potential in the fight against aging. The integration of these approaches could pave the way for more effective and safer anti-aging interventions.

Conclusion:

In conclusion, the pursuit of the fountain of youth has led researchers to explore the potential of rapamycin as an anti-aging intervention. The drug's remarkable effects on lifespan and healthspan in various model organisms have generated excitement about its human applications. However, numerous challenges, such as immunosuppressive properties and potential side effects, must be addressed before rapamycin can become a viable and safe anti-aging therapy. As science continues to advance, the dream of staying younger through the use of rapamycin remains a fascinating avenue for exploration in the quest for healthier aging and extended human lifespans.

[redshift-13]

The first non-invasive biomarker to track and verify efficacy of senolytic drugs

Buck Institute researchers have discovered and are developing a novel, non-invasive biomarker test that can be used to measure and track the performance of senolytics: a class of drugs that selectively eliminate senescent cells. The discovery is expected to play a major role in efforts to develop treatments that would battle a myriad of chronic age-related conditions that range from arthritis to lung disease to Alzheimer’s disease and glaucoma.

[shuga-hill]

Another Win for Senolytics: Fighting Aging at the Cellular Level Just Got Easier

Senolytics, the drug that wipes out senescent cells and a darling candidate for prolonging healthspan, may also be able to rescue cells' energy production.

Longevity research always reminds me of the parable of blind men and an elephant. A group of blind men, who’ve never seen an elephant before, each touches a different part of the elephant’s body to conceptualize what the animal is like. Because of their limited experience, each person has widely different ideas—and they all believe they’re right.

Aging, thanks to its complexity, is the biomedical equivalent of the elephant. For decades, researchers have focused on one or another “hallmark” of aging, with admirable success. For example, we now know that energy production in aging cells goes haywire. Immune responses ramp up, stewing aging tissue in a soup of inflammatory molecules. Dying cells turn into zombie-like “senescent cells,” where they abdicate their normal functions and instead pump out chemicals that further contribute to inflammation and damage.

Yet how these hallmarks fit together into a whole picture remained a mystery. Now, thanks to a new study published in Nature Metabolism, we’re finally starting to connect the dots. In mice, the study linked up three promising anti-aging pathways—battling senescent cells, inflammation, and wonky energy production in cells—into a cohesive detective story that points to a master culprit that drives aging.

Spoiler: senolytics, the drug that wipes out senescent cells and a darling candidate for prolonging healthspan, may also have powers to rescue energy production in cells. 

Let’s meet the players.

From Metabolism to Zombie Cells

Individual cells are like tiny cities with their own power plants to keep them running. One “celebrity” molecular worker in the process of generating energy is nicotinamide adenine dinucleotide (NAD). It’s got a long name, but an even longer history and massive fame.

Discovered in 1906, NAD is a molecule that’s critical for helping the cell’s energy factory, the mitochondria, churn out energy. NAD is a finicky worker that appears on demand—the cell will make more if it needs more; otherwise, extra molecules are destroyed (harsh, I know). As we age, our cells start losing NAD. Without the critical worker, the mitochondria factory goes out of whack, which in turn knocks the cell’s normal metabolism into dysfunction.

At least, that’s the story in mice. Although yet unproven for slowing aging or age-related disorders in humans, NAD boosters are already making a splash in the supplement world, raising even more need to understand how and why NAD levels drop as we age.

Giving NAD a run for its anti-aging fame are senolytics, a group of chemicals that destroy senescent “zombie” cells. These frail, beat-up cells are oddities: rather than dying from DNA damage, they turn to the dark side, staying alive but leaking an inflammatory cesspool of molecules called SASP (senescence associated secretory phenotype) that “spread” harm to their neighbors.

A previous study in ancient mice, the equivalent of a 90-year-old human, found that wiping out these zombie cells with two simple drugs increased their lifespan by nearly 40 percent. Others using a genetic “kill switch” in mice found that destroying just half of zombie cells helped the mice live 20 percent longer, while having healthier kidneys, stronger hearts, luscious fur, and perkier energy levels. Similar to NAD supplements, pharmaceutical companies are investigating over a dozen potential senolytics in a race to bring one to market.

But what if we can combine the two?

A Hub for Aging

The new study, led by aging detectives Drs. Judith Campisi and Eric Verdin at the Buck Institute for Research on Aging in Novato, California, asked if we can connect the line between NAD and zombie cells, like suspects on an evidence board.

Their “lightbulb” clue was a third molecule of interest, highlighted in a 2016 study. Meet CD38, a molecule that plays double roles as an aging culprit. It wreaks havoc as an immune molecule to boost inflammation, while chewing up and destroying NAD. If CD38 is a new drug flooding the streets, then the team’s goal is to hunt down where it came from.

Using tissue from both mice and humans, the team traced CD38 to a type of immune cells. These cells, called M1 macrophages (literally, “big eaters”) are well known to increase inflammation in the body and cause DNA damage with age. When comparing fat tissue isolated from young and old mice, the team realized that these over-hyper immune cells pump out CD38 like crazy as the cells age—which, in turn, breaks down the good-for-you molecule, NAD.

One mystery in aging, explained Verdin, is whether NAD levels drop because of a faucet problem—our ability to make NAD—or leaky sink problem, where aging cells break down NAD too fast. “Our data suggests that, at least in some cases, the issue stems from the leaky sink,” he said.

The Zombie Connection

Here’s the evidence so far: aging triggers a type of immune cells to pump out CD38, a nasty chemical from immune cells that eats up NAD. But why? More importantly, how can we stop it?

In an unexpected twist of events, the connection seemed to be zombie cells.

Remember, zombie cells leave a chemical evidence trace of inflammatory chemicals called SASP. They also change their “molecular look” so it’s possible to tease them out from a sea of healthy cells (think zombies versus humans in any zombie movie). In fatty tissue from aged mice, the team identified zombie cells and found that their “toxic waste” massively increased the amount of CD38 floating around. Going back to the drug analogy, if CD38 is a drug, then the specific immune cells are the manufacturers pumping it out to eat up NAD and wreck the cell’s energy production. Here, zombie cells are the drug kingpin, and their SASP molecules direct immune cells to make more CD38.

Frozen in Time

If zombie cells are the kingpin, then getting rid of them should reduce the inflammatory CD38 “drug,” and in turn, preserve good guy NAD. To test it out, the team used a genetically engineered mouse, which allows scientists to identify zombie cells and selectively kill them off.

The team injected the mice with a drug that damaged their DNA. This mimics aging, in the sense that it increased zombie cells and CD38. Killing zombie cells lowered CD38 levels—like clearing a drug off the streets—and preserved NAD.

Voilà—case solved!

“We are very excited to link two phenomena which have been separately associated with aging and age-related disease,” said Verdin.

For now, zombie cells seem to be a master-level culprit that drives inflammation, decreases NAD levels, and breaks the cell’s energy production. This suggests that senolytics, which selectively kills off zombie cells, could as a secondary effect also increase NAD—something we didn’t know previously.

To Verdin, however, that doesn’t mean NAD supplements are useless or that senolytics are the one-and-only silver bullet against aging. “Ultimately I think supplementation will be part of the equation, but filling the sink without dealing with the leak will be insufficient to address the problem,” he said. In other words, for NAD supplementation to better work, we may need to also use senolytics to decrease zombie cells and CD38 levels, thus “plugging the leak.”

If all this makes your head spin—yup, same here! Our bodies run multiple “aging programs,” and we’ve just begun linking all these disparate culprits together. But the rewards could be great for creating therapies that slow or even reverse aging. After all, if we can find several masters that drive aging, why go after the little guys when you can target the boss?