The Ultimate Guide to Senolytics

Senolytics is a field of scientific research that focuses on cellular senescence (more on this below) with the aim of having fewer senescent cells in the body. And it could be about to completely revolutionize the anti-aging industry. In this guide, you’ll find everything you need to know about senolytics and the benefits scientists are currently discovering.

What are senolytics?

Senolytics are compounds that help the body in removing senescent cells.

Senescent cells are cells within the body that have stopped dividing or regenerating. While they’re not dead or dying so to speak, they are somewhat stuck in a zombie-like state.

With these ‘zombie cells’ sticking around, different plaques build up and have an impact on other cells and tissues around them. This can cause age-related ailments like inflammation, cardiovascular disease, mitochondrial dysfunction and Alzheimer’s. As we age, senescent cell abundance become a bigger problem and can significantly contribute to the aging process.

So, the big question is, can senolytics reverse aging?

As with most supplement products, there’s research to suggest both sides of the argument. Just like some might swear by applying anti-aging cream, others think it’s a money-making marketing ploy.

Senolytic research is being published thick and fast, with various clinical trials suggesting senolytic supplements can prevent, reverse, or slow down the aging process – ultimately extending your life.

Senolytics and senescent cell elimination could also become a popular option for targeting specific cells that are causing chronic illnesses like cancer. This could in turn help to slow down the growth of cancer cells – making treatment much easier to manage.

The area of senescence associated secretory phenotype (SASP) is a key concept in the study of cellular senescence, which occurs when cells stop dividing and enter a state of permanent growth arrest. SASP refers to the secretion of a variety of pro-inflammatory cytokines and other proteins that are associated with the onset of cellular senescence. These secreted proteins play an important role in the communication between senescent cells and their surrounding environment and are believed to be involved in the process of aging. The senescence associated secretory phenotype is a key concept in the study of cellular senescence, which occurs when an aging cell stops dividing and enters a state of permanent growth arrest. SASP refers to the secretion of a variety of pro-inflammatory cytokines and other proteins that are associated with the onset of senescence. These secreted proteins play an important role in the communication between senescent cells and their surrounding environment and are believed to be involved in the process of aging.

Senescence associated secretory phenotypes

Senescence associated secretory phenotypes (SASPs) are a set of secreted proteins, cytokines, and other molecules that are released by senescent cells. These molecules act as signals to neighboring cells, and can have a range of effects including promoting inflammation, altering cell behavior, and inhibiting tissue regeneration.

The senescence associated secretory phenotype is thought to be an evolutionary adaptation that allows senescent cells to alert their neighbors of their presence and trigger an immune response. This can help protect against the development of cancer cells, as senescent cells are no longer able to divide and would otherwise accumulate in the body and contribute to tumor formation. In addition, the SASP may also aid in the removal of damaged and dysfunctional cells, which can contribute to again. Furthermore, the SASP may have a role in the promotion of tissue repair and regeneration, as some proteins secreted by senescent cells can stimulate stem cell activity and help to replenish damaged tissue.

Natural killer cells and senescence

Natural killer (NK) cells are a type of white blood immune cell that are important for controlling infection and helping the body to fight cancer. They are also known to play a role in the process of senescence. NK cells have been shown to act as an important regulator of senescence, as they can promote senescence in some cells while inhibiting it in others. For instance, NK cells have been found to promote senescence in cancer cells, which helps to prevent the growth and spread of tumor cells. In addition, NK cells may play a role in the aging of normal cells, as they can promote the senescence of cells that are no longer useful or are damaged. Thus, NK cells are important for both preventing cancer and controlling the aging process.

Age related diseases and senescence

As a person ages, the number of senescent cells in the body increases. This accumulation of senescent cells can lead to age-related diseases such as cancer, heart disease, and alzheimer's. To reduce the amount of senescent cells accumulating in the body, researchers are using various therapies that target and remove senescent cells. These therapies include senolytic drugs, which target and destroy senescent cells, and gene therapies, which help to prevent the formation of such senescent cells.

Cellular senescence

Cellular senescence is a process in which cells stop replicating and enter a state of permanent cell cycle arrest. It is an important mechanism for limiting the proliferation of damaged or altered cells, as it prevents them from becoming cancerous or leading to multiple chronic diseases. Senescent cell accumulation increases as we age Senescence can be triggered by a variety of factors, such as stress, damage to DNA, certain infections, and even aging. In senescent cells, a number of molecular changes occur, such as increased expression of certain proteins and altered gene expression. These changes lead to a decrease in the cell’s ability to divide, thereby leading to cell cycle arrest. Senescent cells can also secrete molecules and signal to other cells that may lead to inflammation and other health problems.

What are senescence markers?

Senescence markers are molecules that are used to measure the level of cell senescence in a particular cell type. These markers include proteins, lipids, and other molecules that are associated with the aging process, such as telomere length, p16INK4a, and senescence-associated beta-galactosidase (SA-β-gal). These senescent cell markers are used to measure the age of a cell, as well as to identify cells that are undergoing senescence, which is a process of irreversible growth arrest. Additionally, senescence markers can be used to study the effects of aging on cells and tissues, as well as to identify compounds that may delay or reverse the aging process.

Senescence markers can also be used to detect the onset of age-related disorders. For example, markers of senescence have been found to be higher in patients with Alzheimer’s disease, and can be used to diagnose the condition in its early stages. Furthermore, senescence markers can be used to monitor the effectiveness of treatments for age-related conditions. By monitoring the levels of senescence markers, physicians can ensure that the treatment is targeting the right areas, and can make adjustments if necessary. The use of senescence markers is also important for understanding the aging process as a whole, as they can be used to identify the mechanisms behind the onset of age-related diseases. Additionally, senescence markers have been studied for their potential role in identifying individuals who may be at a higher risk for age-related diseases. By understanding the markers associated with aging, researchers can develop more targeted preventive measures.

What is senolytics therapy?

Biotech and pharmaceutical firms like Unity Biotechnology, Oisin, and SIWA Therapeutics are already one step ahead and are pioneering the way to senolytic therapy with various clinical trials underway. Rather than just focusing on creating daily supplements, these top teams are looking at how to kill senescent cells by undertaking gene therapy every few years designed for eliminating senescent cell burden around the body.

The benefits of senolytics

As mentioned above, the benefits of senolytics are still being researched. But some incredible benefits have already been discovered.

Their main benefit comes from reducing the risk or preventing diseases associated with aging and improving metabolic function. This reduction can then have a domino effect on other elements of the aging processes. For example, senolytics can be linked to improved physical and mental function and a longer lifespan.

Of course, it’s not just about living longer. Senolytics aim to not just keep people around longer, but also to keep them healthier for years to come. A human’s ‘health span’ is the amount of time a person lives without pain or suffering. Senolytics have the potential to increase this health span, allowing people to enjoy a fuller life for years to come.

Deep research into senolytics, could make tidal waves of change for economies and healthcare industries around the world.

With an aging population, you can see the pressures on the healthcare sector in so many countries. Age-related illnesses take up a lot of resources, time, and treatment. If there is a way to increase the health span for the older generation, there could be a chance to ease the pressure on services we all depend on.

Fewer chronic ailments such as arthritis and inflammation could also allow people to stay at work for longer. This would have a significant impact on the economy – both in terms of business, as well as government benefit funding.

How do senolytics work?

In order for us to have a long, happy and healthy life, we need to keep cell regeneration around the body active for as long as possible. Cell regeneration is key to maintaining organs, bones, and different bodily systems (digestive, cardiovascular, etc.).

Within the regeneration process, our cells divide, regenerate, and even get replaced by stem cells or newer versions. Without knowing it, your body is constantly regenerating its own cells. Regeneration is what allows the skin to heal after a cut or injury, and is why we can continue to donate blood without impacting our own supplies.

Through the natural process of aging, cell regeneration slows or becomes disrupted. When this happens, and aging cell enters a state of ‘senescence’ which is often described as the ‘zombie state’ we mentioned above. What’s most concerning, is that ac senescent cells accumulate, they can emit chemicals that cause surrounding cells to enter a senescence state too.

To target senescent cells, the body uses a process called apoptosis, which is part of the immune system. As with all the systems in our aging body, the immune system can slow down and become less effective. This means senescent cells are more likely to stay in the body, rather than be removed.

Which is where senolytics come in handy. These drugs can selectively eliminate senescent cells, prevent them building up and stop other cells entering cellular senescence. By removing zombie cells, senolytics help to promote healthier tissues and organs – ultimately slowing down the aging process.

Senolytics essentially act as a big cell detox – much more effective than a quick green smoothie.

Examples of senolytics

If you’ve never heard of senolytics, it can be difficult to know where to start. Below are a few examples of senolytic compounds, as well as senolytic foods you might want to start introducing into your diet.

Fisetin

Fisetin is a flavonoid antioxidant that’s often referred to as the leading senolytic supplement on the market and has been shown to be effective at eliminating senescent cells. Fisetin is actually an ingredient within the supplements and is the most potent senolytic available. It’s found in plant-based products like strawberries, apples, grapes, and mangoes. But it’s found in such small amounts naturally, you couldn't absorb the correct dose by chomping on a fruit salad. An effective dose would need to be around 100 mg a day, while the average diet only includes 0.4 mg.

Research shows Fisetin to be effective in as a method to selectively clear senescent cells, reducing inflammation and glycation and increasing the production of protective cells.

Is quercetin a senolytic?

Quercetin is another prominent senolytic that’s part of the flavonoid family with eliminating senescent cell properties. Derived from the Japanese ‘pagoda tree’, it’s found to be particularly effective when combined with zinc or theaflavin. Quercetin is already a treatment for chronic illnesses like cardiovascular disease or prostatitis. It is also known to help with cystitis, viral infections, and even seasonal allergies.

As with any medication, quercetin can come with side effects. Though nothing too scary. Common side effects include headaches, nausea, and shortness of breath. Some may also experience numbness or tingling. In rare cases, the medication could lead to kidney damage.

You can absorb quercetin through green tea, coffee, berries, and citrus fruits. It can also be found in red wine if you enjoy a tipple from time to time. That said, you couldn't consume the amount of quercetin needed for the clearance of senescent cells from these foods entirely.

Is curcumin a senolytic?

Curcumin, which can be found in turmeric, is commonly linked to anti-ageing. Turmeric boasts plenty of benefits like improving cognition and memory. Curcumin itself can extend the lifespan of mice and fruit flies, with one study finding a fruit fly's life could be prolonged by up to 26%. Curcumin acts as a neuroprotective agent which can alleviate symptoms for diabetes, cancer, or atherosclerosis sufferers, too.

Is resveratrol a senolytic?

Resveratrol is a compound found in plants that’s produced during pathogenic attacks, adverse weather conditions, or environmental stress. You can find the compound in over 70 types of plants including mulberries, grapes (in the skin, rather than the flesh), and peanuts. Its presence in red grapes could be why red wine is often considered to have cholesterol-lowering benefits.

In the 2003 journal Nature, Howitz and Sinclair found that resveratrol could extend the lifespan of certain yeast species. This was later followed up by a similar experiment with worms and fruit flies. In 2006, a team in Italy was able to establish a positive link between resveratrol dosage and higher swimming activity, risk avoidance, and extended lifespan in fish. Sinclair then continued his studies and found positive results in mice.

What are the best senolytic supplements?

From a single-ingredient perspective, based on all the research done so far, fisetin and quercetin are often classed as the best and most effective senolytics for cellular senescence.

At Longevity Box we have taken these two senescence power-houses and combined them with a combination of 6 other senescence-promoting compounds to create our proprietary Senolytic 8 formula.

Are there any senolytic side effects?

Like quercetin, a lot of senolytics can come with potential side effects including nausea and diarrhea. In rare cases, those taking senolytics can suffer from kidney damage, and there’s always the chance of an allergic reaction.

With any supplement, it’s a wise idea to speak to your doctor about possible side effects, as well as any other medications you’re currently taking. You also want to make sure you’re generally healthy so that you have the highest chance of avoiding any side effects.

Can you clear senescent cells naturally?

In younger generations, the immune system takes care of targeting senescent cells quickly and effectively. When these functions start to slow down, senescent cells can start to build up and become a problem.

Of course, the easiest way of reducing senescent cell burden is to maintain a healthy lifestyle. If you’re young, eating a varied, balanced diet, sleeping well, and exercising regularly, you shouldn’t need to take extra supplements.

Anything that boosts your immunity will keep you in good shape throughout the aging process and help in clearing senescent cells.

Does fasting clear senescent cells?

Intermittent fasting has become incredibly popular over the past few years. Millions claim that it’s changed their lives for the better. Interestingly, studies show that intermittent fasting can also promote a longer lifespan.

Stimulating a process called autophagy – in which cells digest themselves – has been found to be an effective way to induce senescence. Autophagy can be initiated through fasting or calorie restriction, so this could be a natural option for those looking to get ahead of senescent cells.

Is exercise a senolytic?

Exercise is often linked to anti-aging and overall health. However, the jury is still out on whether it’s a senolytic. In general, regular exercise is never deemed to be a bad thing and should be encouraged for everyone at any age. Exercise brings plenty of benefits – both physical and mental – and can keep our bodies functioning in all the right ways.

Where can I buy senolytic drugs?

Senolytic drugs are becoming more popular, and so their availability is increasing. Whilst pharmaceutical and biotech companies focus on developing prescription-based senolytics, we at Longevity Box believe supplements are a powerful interim alternative. Our Senolytic 8 supplement contains a strong dose of both fisetin and quercetin, so it is a great option to get started with.

How to use senolytic drugs

We recommend that senolytics are only used by those over 40, who have consulted their doctor first. When they hit the market, you will be able to use the drug if you're already suffering from age-related ailments, or if you want to try prevent them altogether.

The drugs will be able to be taken regularly with food, or when you feel like it’s needed.

Final thoughts

Senolytics is in an exciting phase of growth and development. While we wait to see just how effective these drugs can be in the medical world, start reaping the benefits today with our Senolytics 8 supplement.