The Flavonoids: 

Quercetin, Fisetin and Apigenin

Fisetin, quercetin, and apigenin belong to a group of plant-based chemicals called flavonoids. These ingredients are most known for their ability to clear senescent cells, reduce inflammation, and bolster NAD levels. Oh, and they may promote a smooth mood and even smoother skin.

Flavonoids are a group of plant-derived substances that plants rely on to protect themselves and help regulate metabolism. Luckily, although we’re not as delightfully whimsical as our plant friends, these same flavonoids offer us a similar “flavor” of benefits (see what we did there?).

Quercetin, fisetin, and apigenin are all known for their potent anti-inflammatory properties and ability to reduce oxidative stress via several different pathways. Since inflammation is one of the root causes of most diseases (including aging), we think this is a pretty big deal.

Quercetin and apigenin also promote healthier NAD+ levels, which naturally decline as we age. NAD+ is a critical coenzyme in our bodies that is necessary for producing cellular energy and repairing DNA. Quercetin and apigenin work to prevent the breakdown of NAD+ by the enzyme CD38, thus protecting these fundamental metabolic processes.

In addition, studies have shown that fisetin and quercetin can clear senescent cells (“the hecklers”) to reduce inflammation and improve stem cell activity. This promising potential to eliminate those nasty senescent cells has a LOT of people talking about these two flavonoids.

Some other fun facts about our favorite flavonoids:

• Studies have shown that apigenin (most commonly found in chamomile tea) can decrease the symptoms of anxiety and depression in humans. Who knew that tea could have such life-changing effects?
• Fisetin and quercetin may reduce wrinkles in the skin by slowing down collagen breakdown.

CurcuPrime® (Tetrahydrocurcumin – 4HC)

Curcumin is one of the most-studied and longest-loved longevity-promoting ingredients because of its strong anti-inflammatory and antioxidant properties. However, in the past, curcumin’s poor bioavailability made it challenging to get high enough doses through oral supplementation. Luckily, CurcuPrime® by NNB has solved that problem, giving you the same benefits of curcumin but with better absorption and bioactivity.

Do you ever feel like Mother Nature is playing tricks on us, secretly laughing behind those weeping willows? We think that curcumin may be one of her favorite tricks.

Curcumin is a bright yellow polyphenol derived from turmeric root. It has been used for hundreds of years and possesses multiple alleged superpowers, including antioxidant, anti-inflammatory, anti-cancer, anti-microbial, and anti-pain properties.

In humans, curcumin has been shown to improve memory and brain function, improve lipids (including LDL oxidation), and reduce blood sugars.

In addition, multiple animal models have shown that curcumin can extend lifespan by as much as 26%! We can likely credit this impressive increase to curcumin’s potent antioxidant, anti-inflammatory, and blood sugar regulation abilities, its promotion of longer telomeres, and its elimination of senescent cells. Whoa!

So, how is any of this a trick? It sounds pretty great, right?

So, how is any of this a trick? It sounds pretty great, right?

It’s a “trick” because traditional curcumin has low bioavailability when taken orally because of its rapid breakdown, which means very little of it gets or stays in the body.

Luckily, CurcuPrime® (tetrahydrocurcumin), the branded ingredient in HOP Box, resolves the poor bioavailability of traditional curcumin by offering a longer-lasting, more active form of this long-loved ingredient.

And, if you’re wondering which of the Downfalls of Aging curcumin directly supports, the answer is ALL of them. Isn’t Mother Nature the coolest!

Downfalls of Aging affected by CurcuPrime®:

• All of them!!

Astaxanthin

Astaxanthin is the Queen of antioxidants and may protect the eyes and skin against UV damage, slow brain aging, and promote a healthier heart, stronger muscles, and less painful joints.

It wouldn’t be a stretch to call astaxanthin the Queen of the Antioxidants, given that this particular nutrient is 500 times stronger than vitamin E and 6000 times more potent than vitamin C at subduing oxidative stress.

Found naturally in microalgae, yeast, and some types of fish, astaxanthin can be tricky to incorporate into your diet in sufficient amounts. However, supplementing with this antioxidant is well worth the effort, since she has her Queenly fingers in many pies when it comes to slowing aging and bolstering beauty.

Astaxanthin is probably most known for its benefits to the eyes, where it’s been shown to protect against UV damage, decrease eye strain, and improve visual acuity in its users.

Similarly, astaxanthin is well-loved for its skin effects. Studies have shown that this antioxidant protects the skin from UV damage and promotes the repair of damaged and aging skin, helping with everything from skin hydration and elasticity to age spots and wrinkles.

A recent study in adults also found that supplementing with astaxanthin daily may slow brain aging and promote improvements in memory.

Finally, astaxanthin may improve cardiovascular and immune health while promoting stronger muscles and less painful joints.

So, yeah. Astaxanthin is a total Queen, and we’re excited to feature it in our all-star HOP Box line-up!

Downfalls of Aging affected by Astaxanthin:

• Unstable Mabel (Genomic instability)
• Moodie Foodie (Deregulated nutrient sensing)
• Free O’Charge (Mitochondrial dysfunction)
• The Heckler (Cellular senescence)

NR

Supports energy production, healthy metabolism, and muscle strength by boosting cellular NAD levels.

If you’ve spent much time looking into “longevity-promoting supplements,” you’ve likely run into NMN or NR, both of which have gained attention for their potential to enhance healthspan and lifespan. NR (Nicotinamide Riboside) is a naturally occurring precursor to NAD (Nicotinamide Adenine Dinucleotide), a vital molecule for cellular energy production and DNA repair.

NAD is crucial, but as you age, its levels decline. NAD is a big deal, but by the time you’re forty, you have half as much as when you were younger.

A daily dose of oral hyaluronic acid has also been shown to:

• NAD improves the function of our mitochondria, so you can swim for two hours and still have enough energy to climb out of the pool.
• It helps repair DNA and protects the epigenome, so you aren’t forever tormented by one night’s worth of bad decisions.
• It improves stem cell health and signaling, so you can heal like Wolverine instead of sinking like a submarine.

In humans, NR supplementation (via its boosting effect on NAD) has been shown to lower inflammation, improve insulin sensitivity, positively affect metabolism, and improve muscle strength and performance.

And, don’t get us started on what NR can do in animal models. In animal studies, NR supplementation has increased cognition and memory, slowed ovarian aging, improved fertility, increased stamina, and lengthened lifespan.

NR occurs naturally in food, but it would take A LOT of milk and brewer’s yeast to replace the NAD lost during the normal aging process. Luckily, studies have shown that supplementing with the dose of NR found in the HOP Box (250mg twice daily) adequately boosts blood NAD levels AND is safe for humans. Woo hoo!

Downfalls of Aging affected by NR:

• Moodie Foodie (Deregulated nutrient sensing)
• Life Sticks (Epigenetic alteration)
• Free O’ Charge (Mitochondrial dysfunction)
• Unstable Mable (Genomic instability)
• The Heckler (Cellular senescence)
• Old Man Stem-y (Stem cell exhaustion

Puremidine®

By activating cellular autophagy, spermidine promotes healthy cell renewal – think “Spa Day for your cells” – promoting skin and hair benefits, as well as improved longevity.

Predicted by longevity researcher Dr. David Sinclair to be THE longevity supplement of 2022, spermidine has quickly made a name for itself, despite getting a rocky start as “the one that is found in semen.”

Yes, spermidine is found in semen. But, that’s no surprise because this natural polyamine is found in EVERY cell in the human body. Unfortunately, levels start to decline after age 30, which is when we often start seeing the effects of aging.

Spermidine is best known for its role in increasing autophagy, which means helping cells recycle and renew themselves. It’s like a spa day for your cells, one where the garbage is taken out, and fresh, rejuvenated, more youthful-acting cells are left behind!

One human epidemiological study found that those with a diet higher in spermidine lived an average of more than five years longer than those with low spermidine diets. Other studies have found that spermidine decreases hair loss, improves skin health, and may boost memory in older folks with Alzheimer’s disease.

And that’s not all! Multiple animal studies have shown that spermidine increases longevity (by as much as 25%), protects the heart, improves memory, boosts fertility, and promotes weight loss and muscle maintenance.

Natural sources of spermidine include broccoli, cauliflower, and wheat germ. The spermidine in our HOP Box (Puremidine®) is special because it’s unadulterated and ultra-pure, meaning that you take a fraction of the dose of other brands and still see significant benefits.

Downfalls of Aging affected by spermidine:

• Unstable Mabel (Genomic instability)
• Shorty T (Telomere attrition)
• Free O’ Charge (Mitochondrial dysfunction)
• The Heckler (Cellular senescence)
• Old Man Stem-y (Stem cell exhaustion)

Calcium Alpha Ketoglutarate (CaAKG)

CaAKG acts as a metabolic and longevity switch in humans and has been shown to markedly affect healthspan and lifespan in animals, resulting in less graying, fat reduction, and increased vitality.

If you could see pictures of the rickety, overweight, graying mice who turned into vibrant, slim, black-haired super-mice by taking CaAKG with their food every day, you MIGHT just understand why we’re so excited about this one!

Alpha Ketoglutarate (AKG) is a naturally-occurring intermediate of the TCA cycle in your cells, which means it’s needed for your cells to turn food into energy.

Between age 40 and 80, your AKG levels decrease tenfold. And, unlike many other longevity molecules, this one is NOT found in the human diet. You can boost levels by caloric restriction (fasting), or you can supplement.

In humans, AKG has been shown to reduce DNA methylation damage. In fact, one study using the calcium form of AKG (CaAKG) showed that this supplement turned back the epigenetic (“biological age”) clock by seven years in both women and men!

Aside from improving mitochondrial energy production, AKG helps us maintain metabolic flexibility so we can eat a variety of foods and still have healthy metabolic responses. Researchers have also found that AKG improves skin health in animals and humans by increasing collagen and elastin production and improving wrinkles, hydration, and skin barrier function.

Finally, in a major mouse study, AKG supplementation not only increased lifespan, but it also improved HEALTHSPAN by more than 40%, which meant less frailty, less obesity, and gray-brittle hair turning shiny and black.

Downfalls of Aging affected by CaAKG:

• Life Sticks (Epigenetic alteration)
• Free O’Charge (Mitochondrial dysfunction)
• Gossip Guuurl (Altered intercellular communication)
• Old Man Stem-y (Stem cell exhaustion)

Magnesium Glycinate

Needed for more than 500 reactions within the body, magnesium doesn’t just help with stress and sleep. It also promotes healthy aging by helping to repair DNA, increasing cellular energy, and reducing inflammation. Go Mag!

“Yes, but did you check her magnesium level?”

When Dr. Amy Killen was in medical school, her Internal Medicine attending physician was a magnesium researcher. He believed that almost all of the problems coming through the hospital doors were caused or exacerbated by insufficient magnesium.

At the time, Dr. Killen thought he might be a little crazy.

But, it turns out that magnesium is necessary for more than 500 enzymes in the body! Not to mention that chronically low magnesium can increase the risk of everything from high blood pressure, heart disease, and type 2 diabetes to osteoporosis, depression, and insomnia.

Oh, and up to 70% of people have magnesium deficiency!

Magnesium is most known for its ability to improve sleep, reduce anxiety and bring on those calm, “ahhhh” moments of pure relaxation.

But, this mineral, found in a variety of foods, may also promote longevity since it is a key factor in repairing DNA damage, increasing cellular energy, and reducing inflammation.

Dr. Killen would like to take back any bad things she said or thought about that magnesium-fanatic attending physician of hers. It turns out, he actually knew a thing or two about how to stay healthy!

Downfalls of Aging affected by magnesium glycinate:

• Unstable Mabel (Genomic instability)
• Free O’ Charge (Mitochondrial dysfunction)
• Gossip Guuurl (Altered intercellular communication)

The Flavonoids: 

Quercetin, Fisetin and Apigenin

Fisetin, quercetin, and apigenin belong to a group of plant-based chemicals called flavonoids. These ingredients are most known for their ability to clear senescent cells, reduce inflammation, and bolster NAD levels. Oh, and they may promote a smooth mood and even smoother skin.

Flavonoids are a group of plant-derived substances that plants rely on to protect themselves and help regulate metabolism. Luckily, although we’re not as delightfully whimsical as our plant friends, these same flavonoids offer us a similar “flavor” of benefits (see what we did there?).

Quercetin, fisetin, and apigenin are all known for their potent anti-inflammatory properties and ability to reduce oxidative stress via several different pathways. Since inflammation is one of the root causes of most diseases (including aging), we think this is a pretty big deal.

Quercetin and apigenin also promote healthier NAD+ levels, which naturally decline as we age. NAD+ is a critical coenzyme in our bodies that is necessary for producing cellular energy and repairing DNA. Quercetin and apigenin work to prevent the breakdown of NAD+ by the enzyme CD38, thus protecting these fundamental metabolic processes.

In addition, studies have shown that fisetin and quercetin can clear senescent cells (“the hecklers”) to reduce inflammation and improve stem cell activity. This promising potential to eliminate those nasty senescent cells has a LOT of people talking about these two flavonoids.

Some other fun facts about our favorite flavonoids:

• Studies have shown that apigenin (most commonly found in chamomile tea) can decrease the symptoms of anxiety and depression in humans. Who knew that tea could have such life-changing effects?
• Fisetin and quercetin may reduce wrinkles in the skin by slowing down collagen breakdown.

Vitamin D3

Most of us don’t get enough vitamin D these days, since this vitamin gets produced when we expose our skin to the sun. Luckily, HOP has you covered! Vitamin D3 is a crucial vitamin/hormone for creating strong bones as well as a healthy brain, heart, and immune system.

Did you know that in the “old days,” people with chronic diseases would often visit sanitariums where they would sit outside in lawn chairs, basking in the sun, engaging in “heliotherapy” as a way to hasten healing?

Heliotherapy means “sun therapy,” and many of its benefits come from the sun’s ability to boost vitamin D levels within the body.

Vitamin D is both a vitamin that can be found in foods (such as seafood and meats) and a hormone that gets activated when UV light hits our skin.

We know that low vitamin D contributes to many age-related diseases, including cardiovascular disease, obesity, diabetes mellitus type 2, and cancer. Unfortunately, because of concerns about skin damage from the sun, as well as indoor jobs and not-so-sunny climates, many of us don’t get nearly enough vitamin D in our everyday lives.

Vitamin D is best known for its ability to usher calcium and phosphorus into bones, helping to keep bones strong, which is especially important as we age.

But vitamin D is much more than a “bone” hormone. Studies have shown this vitamin to be helpful for everything from protecting the brain and reducing depression symptoms to bolstering the immune system and keeping the heart and blood vessels healthy.

Finally, vitamin D also appears to play a role in slowing telomere aging, likely because of its anti-inflammatory effects. Most notably, it has been shown in animals to increase lifespan by up to 33%!

Downfalls of Aging affected by vitamin D3:

• Unstable Mabel (Genomic instability)
• Protein Misfit (Loss of proteostasis)
• Life Sticks (Epigenetic alteration)
• Free O’Charge (Mitochondrial dysfunction)
• Old Man Stem-y (Stem cell exhaustion)

Vitamin K2-MK7

Vitamin K activates specific “Robin Hood-esque” Gla-proteins that move calcium away from blood vessels, where it’s not wanted, and into bones, where it is. Strong bones and supple blood vessels – now that’s a story worth telling!

Originally known as the “Koagulation” vitamin because of its importance in blood clotting, vitamin K has now jumped into the longevity limelight for its ability to protect bones and blood vessels.

Vitamin K activates a series of proteins in the body called “Gla-proteins.” These Gla-proteins are necessary for directing calcium INTO the bones and OUT OF the blood vessel walls. 

We like to think of these Gla-proteins, which require activation by vitamin K, as being a bit like Robin Hood, taking calcium out of the areas that don’t need it (the blood vessels) and putting it in places that really really need it (the bones).

Because of this “Robin Hood” effect with calcium, people who take in higher amounts of vitamin K have been shown to have lower risks of osteoporosis and fracture and lower risk of coronary artery disease than people who don’t consume much vitamin K. 

Similar to those with low levels of vitamin D (another fat-soluble vitamin), people with low levels of vitamin K are at increased risk for cardiovascular disease, type 2 diabetes, metabolic syndrome, and cancer. Consuming more Vitamin K can combat these same outcomes.

Finally, vitamin K is a powerful antioxidant and strong anti-inflammatory. This may explain why epidemiological studies show that people with the highest vitamin K intake have the lowest overall mortality rates.The form of vitamin K that is the most bioavailable and longest lasting in the body is called vitamin K2-MK7, which is what you’ll find in the HOP Box.

One word of warning:  People taking blood thinners such as Coumadin should not take vitamin K without discussing it with their doctors.

Downfalls of Aging affected by vitamin K2-MK7:

• Unstable Mabel (Genomic instability)
• The Heckler (Cellular senescence)
• Gossip Guuurl (Altered intercellular communication)

GlucoVantage® (Dihydroberberine)

The GlucoVantage® inside HOP Box is five times more bioavailable and lasts twice as long as traditional berberine, which means more of berberine’s “secret sauce” gets to the cells. Studies have shown that berberine promotes reductions in blood sugar, insulin, and fat storage due to its activation of the longevity-promoting AMPK cellular pathway.

Have you ever had a secret that was SO good you almost didn’t want to share it? Well, berberine might just be longevity medicine’s best-kept secret, and we want to yell it from the rooftops.

Berberine is naturally found in a variety of plants and is best known for its ability to reduce blood glucose (sugar) and insulin levels.

Chronically elevated blood glucose is an indicator of cells’ inability to take in and use energy effectively and a major cause of metabolic syndrome and inflammation in the body.

Put another way, high blood sugar, even in non-diabetics, makes us age faster!

Berberine not only improves how our cells use glucose but has also been shown to shuttle glucose to muscles instead of fat cells, which may assist with fat loss over time.

Berberine’s fat-burning, sugar-lowering properties stem from its ability to activate a cellular enzyme called AMPK. We can also activate AMPK through exercise and caloric restriction, two other longevity-promoting practices known to improve metabolic health.

This effect is a big deal since more than 70% of Americans are pre-diabetic or diabetic, and more than 85% of us are metabolically unhealthy.

Traditional berberine, although fabulous, is poorly absorbed and often causes gastrointestinal upset (not so fabulous!). However, the dihydroberberine (GlucoVantage®) found in HOP Box is five times more bioavailable than traditional berberine, lasts twice as long in the blood, and doesn’t cause the same stomach upset.

See, we told you this was a secret worth telling!

Downfalls of Aging affected by GlucoVantage®:

• Life Sticks (Epigenetic alteration)
• Moodie Foodie (Deregulated nutrient sensing)
• The Heckler (Cellular senescence)
• Protein Misfit (Loss of proteostasis)
• Gossip Guuurl (Altered intercellular communication)

NewBiome® (Tributyrin)

A strong, vibrant body depends on a healthy gut. NewBiome®’s tributyrin is a postbiotic that nourishes the cells of the large intestine directly, promoting reduced inflammation, improved immune function, and a better ability to absorb other vital longevity-promoting vitamins and nutrients. Win, win, win!

You’ve heard about prebiotics and probiotics, but have you heard about postbiotics and the many benefits to gut health (and general health) they can provide?

Prebiotics are foods like fiber and fermented foods that provide fuel for the healthy bacteria in your intestines. And since we know we want ALL the good bacteria (and none of the bad ones), another way to increase the levels of these superbugs is to actually consume live bacteria. That’s where probiotics come in.

But why are these “good” bacteria in our gut microbiome so healthy? One of the main ways they help us is by producing short-chain fatty acids (SCFAs) that nourish the cells lining our intestines, thus making our intestinal wall stronger (and, we assume, happier).

So, what if we could jump right past those first few steps and just take in the nourishing SCFAs to feed our intestinal cells and improve our gut health directly?

That’s where NewBiome®’s tributyrin comes in. Each tributyrin molecule delivers three of the SCFAs (butyrate) that are most beloved by our intestinal cells.

By supporting a healthy gut, tributyrin may reduce whole body inflammation, improve immune function, protect the brain and nervous system, and improve metabolism. Oh, and a healthy gut is also necessary for absorbing other longevity-promoting vitamins and nutrients such as the ones you’ll find in the HOP Box!

In the HOP Box, we’ve chosen NewBiome®’s tributyrin because of its high purity, excellent bioavailability, and lack of the typical bad smell and taste of other tributyrin products.

Downfalls of Aging affected by NewBiome®:

• All of them (by improving gut health and absorption)!!

B2, B6, B12, 5-MTHF and TMG

These B vitamins and methyl donors promote healthy brains and blood vessels by acting as methyl group “banks” for thousands of intracellular processes. 

If you’re a little put out by this alphabet soup of nutrients, we don’t blame you. It’s a mouthful of methylation donors if we’ve ever seen one!

Vitamins B2, B6, B12, 5-MTHF (the active form of folate), and TMG (trimethylglycine) do many things, but some of their most important longevity benefits stem from their ability to act as methyl donors.What does this mean?

Have you ever seen those “Take a Penny, Leave a Penny” bowls at the gas station? Where you can take a penny to complete your transaction, or you can leave a penny to help the next person? That penny is kind of like a methyl group. 

In every cell in the body, methyl groups are transferred back and forth between DNA strands, proteins, enzymes, and hormones to regulate everything from your mood and energy levels to how quickly your blood vessels fill with plaque and how fast you can get rid of toxins. Methylation helps repair DNA, protects against cancer, and keeps your immune system healthy.

But, to have enough methyl groups for these many processes, somebody has to “leave a penny,” which is where our B vitamins, 5-MTHF and TMG come in. 

These vitamins are essential for helping to reduce homocysteine levels in the blood, which can significantly reduce the risk of cardiovascular disease. And they are so necessary for optimal brain function that low levels can be associated with actual brain shrinking!

Oh, and did we mention that your body doesn’t store B vitamins, so you need to frequently ingest them in food or as nutritional supplements? 

Downfalls of Aging affected by these methyl donors:

• Unstable Mabel (Genomic instability)
• Shorty T (Telomere attrition)
• Life Sticks (Epigenetic alteration)
• Gossip Guuurl (Altered intercellular communication)