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L-Arginine (Arg) is a proteogenic, semi-essential amino acid: healthy
humans can synthesize L-Arginine using L-Glutamine as a building block;
however, premature infants are unable to produce Arg and additional
supplementation is required for proper growth and development. Arginine
plays pivotal roles in biochemical pathways such as the urea cycle and
the biosynthesis of nitric oxide. Arginine and Ammonia concentrations
are elevated in patients having a mutation in their ARG1 genes. The
mutation causes lower arginase activities – a condition that is known as
Argininemia. Arginine has also been advertised as a supplement due to
its role in the synthesis of nitric oxide, which helps in vasodilation
processes.wisepoqder L(+)-Arginine powder
BioVision's L-Arginine Assay Kit provides a quick, specific, and easy method for the measurement of total L-arginine concentrations in a wide variety of samples. In this enzyme-based assay, L-arginine is converted into a series of intermediates, which will further react with a probe producing a stable colorimetric signal (OD: 450 nm). The kit is simple to use, sensitive and high-throughput adaptable and can detect as low as 1 nmol/well of L-arginine in biological samples.
BioVision's L-Arginine Assay Kit provides a quick, specific, and easy method for the measurement of total L-arginine concentrations in a wide variety of samples. In this enzyme-based assay, L-arginine is converted into a series of intermediates, which will further react with a probe producing a stable colorimetric signal (OD: 450 nm). The kit is simple to use, sensitive and high-throughput adaptable and can detect as low as 1 nmol/well of L-arginine in biological samples.
There are plenty of powerful new drugs to help prevent and treat chronic
health problems. But we also know that certain nutrients may help, as
well. Take arginine, for example. Arginine has gotten lots of attention
lately for its potential heart benefits. That's important because,
today, about 85.6 million Americans have some form of cardiovascular
disease.wisepoqder Antiaging Powder
Deficiencies of arginine are rare. It's abundant in many different types of foods, and your body can also make it. Arginine-rich foods include red meat, fish, poultry, wheat germ, grains, nuts and seeds, and dairy products. But what does arginine do for the heart, and are there potential side effects?As a natural dietary supplement, arginine has garnered particular attention for its possible heart benefits.
What Are Arginine's Heart Benefits?
In the body, the amino acid arginine changes into nitric oxide (NO). Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation.
Some evidence shows that arginine may help improve blood flow in the arteries of the heart. That may improve symptoms of clogged arteries, chest pain or angina, and coronary artery disease. However, there currently is no data on how the long-term use of arginine affects cholesterol or heart health.Since arginine may help arteries relax and improve blood flow, it may also help with erectile dysfunction.
There are other potential health benefits with arginine, such as possible reduction of blood pressure in some people and improved walking distance in patients with intermittent leg cramping and weakness known as intermittent claudication. However, the scientific studies are not conclusive enough for experts to make any firm recommendations.
Not all studies on arginine have been positive. A 2006 study showed that arginine was not helpful -- and may have been harmful -- for treating heart attacks in combination with standard treatment.
Deficiencies of arginine are rare. It's abundant in many different types of foods, and your body can also make it. Arginine-rich foods include red meat, fish, poultry, wheat germ, grains, nuts and seeds, and dairy products. But what does arginine do for the heart, and are there potential side effects?As a natural dietary supplement, arginine has garnered particular attention for its possible heart benefits.
What Are Arginine's Heart Benefits?
In the body, the amino acid arginine changes into nitric oxide (NO). Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation.
Some evidence shows that arginine may help improve blood flow in the arteries of the heart. That may improve symptoms of clogged arteries, chest pain or angina, and coronary artery disease. However, there currently is no data on how the long-term use of arginine affects cholesterol or heart health.Since arginine may help arteries relax and improve blood flow, it may also help with erectile dysfunction.
There are other potential health benefits with arginine, such as possible reduction of blood pressure in some people and improved walking distance in patients with intermittent leg cramping and weakness known as intermittent claudication. However, the scientific studies are not conclusive enough for experts to make any firm recommendations.
Not all studies on arginine have been positive. A 2006 study showed that arginine was not helpful -- and may have been harmful -- for treating heart attacks in combination with standard treatment.
Senolytics target cellular senescence, a process in which damaged cells,
rather than dying, persist and become toxic to cells around them.
Cellular senescence has been shown to drive multiple age-related
diseases, including idiopathic pulmonary fibrosis (IPF), a chronic,
irreversible and progressive disease that results in scarring of the
lungs. In animal studies, run by Mayo Clinic collaborators James
Kirkland, M.D., Ph.D.; Nathan LeBrasseur, Ph.D., M.S., and Tamara
Tchkonia, Ph.D., senolytics selectively cleared these toxic cells in
mice that model IPF.wisepoqder Quercetin
A lethal disease for which there are few options
"IPF is a devastating and progressive fibrotic lung disease with a median survival of less than five years in newly diagnosed adults usually over 60 years of age," said Anoop M. Nambiar, M.D., M.S., associate professor of medicine at UT Health San Antonio and founding director of the university's Interstitial Lung Disease Program, one of 60 Pulmonary Fibrosis Foundation Care Centers in the United States. Dr. Nambiar is co-first author of the research manuscript and enrolled 12 of the patients at UT Health San Antonio and the South Texas Veterans Health Care System.
Despite the current availability of two U.S. Food and Drug Administration-approved therapies that may slow down disease progression in some IPF patients, the prognosis remains poor and is worse than for many common cancers, Dr. Nambiar said. Lung transplantation may be lifesaving, but often is only an option for younger, healthier patients. "There remains a significant unmet need for safer and better treatments for patients with IPF," Dr. Nambiar said.
Patients enrolled in Texas, North Carolina
In this first-in-human pilot study, the investigators enrolled 14 older adults diagnosed with stable, primarily mild-to-moderate IPF. Participants were enrolled at both UT Health San Antonio, which served as the primary patient recruitment site, and Wake Forest medical school, which initiated the trial and served as the study coordinating center. "Though small, this pilot study marks a major breakthrough in how we treat age-related diseases such as IPF," said Jamie Justice, Ph.D., assistant professor at Wake Forest medical school, co-lead investigator and corresponding study author. "Here, we've therapeutically targeted a fundamental biological hallmark of aging that is implicated in IPF, and we show early but promising results for the first time in human patients. This small study represents a major paradigm shift in treatment strategy."
Each participant received two senolytic drugs, dasatinib and quercetin (DQ), taken by mouth for three consecutive days each week for three consecutive weeks (nine doses total). All patients were able to comply with this regimen without any discontinuation of the study drugs.
The research team measured clinical laboratory chemistries before and after DQ administration, and performed rigorous symptom questionnaires weekly of health, quality of life and side effects to obtain preliminary evidence of safety and tolerability. The team also evaluated markers of physical function including six-minute walk distance, walking speed, sitting-to-standing repetitions, a frailty index based on clinical laboratory chemistries, and biological assays of senescence-associated proteins secreted by the toxic cells.
A lethal disease for which there are few options
"IPF is a devastating and progressive fibrotic lung disease with a median survival of less than five years in newly diagnosed adults usually over 60 years of age," said Anoop M. Nambiar, M.D., M.S., associate professor of medicine at UT Health San Antonio and founding director of the university's Interstitial Lung Disease Program, one of 60 Pulmonary Fibrosis Foundation Care Centers in the United States. Dr. Nambiar is co-first author of the research manuscript and enrolled 12 of the patients at UT Health San Antonio and the South Texas Veterans Health Care System.
Despite the current availability of two U.S. Food and Drug Administration-approved therapies that may slow down disease progression in some IPF patients, the prognosis remains poor and is worse than for many common cancers, Dr. Nambiar said. Lung transplantation may be lifesaving, but often is only an option for younger, healthier patients. "There remains a significant unmet need for safer and better treatments for patients with IPF," Dr. Nambiar said.
Patients enrolled in Texas, North Carolina
In this first-in-human pilot study, the investigators enrolled 14 older adults diagnosed with stable, primarily mild-to-moderate IPF. Participants were enrolled at both UT Health San Antonio, which served as the primary patient recruitment site, and Wake Forest medical school, which initiated the trial and served as the study coordinating center. "Though small, this pilot study marks a major breakthrough in how we treat age-related diseases such as IPF," said Jamie Justice, Ph.D., assistant professor at Wake Forest medical school, co-lead investigator and corresponding study author. "Here, we've therapeutically targeted a fundamental biological hallmark of aging that is implicated in IPF, and we show early but promising results for the first time in human patients. This small study represents a major paradigm shift in treatment strategy."
Each participant received two senolytic drugs, dasatinib and quercetin (DQ), taken by mouth for three consecutive days each week for three consecutive weeks (nine doses total). All patients were able to comply with this regimen without any discontinuation of the study drugs.
The research team measured clinical laboratory chemistries before and after DQ administration, and performed rigorous symptom questionnaires weekly of health, quality of life and side effects to obtain preliminary evidence of safety and tolerability. The team also evaluated markers of physical function including six-minute walk distance, walking speed, sitting-to-standing repetitions, a frailty index based on clinical laboratory chemistries, and biological assays of senescence-associated proteins secreted by the toxic cells.
Researchers have demonstrated that nanoparticles coated with quercetin
molecules can selectively target and eliminate harmful senescent cells.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging.
Senescent cells only make up a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging and cancer; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that often has poor water solubility, chemical instability, or poor bioavailability. These confounding factors could be muddling its effectiveness and making it unreliable as a senolytic therapy. This likely explains why different senolytic studies using quercetin have yielded conflicting results: there are simply too many processes that can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials that quercetin, when used in combination with the cancer drug dasatinib, can be the basis for an effective therapy for eliminating senescent cells. Unfortunately, on its own, quercetin does not have a significant senolytic effect, which is possibly due to its limitations as a polyphenol.
However, there are ways to overcome these issues with quercetin and other similar polyphenols, and that is by using special delivery systems that make the molecules more effective and controllable. Polymer nanoparticles, lipid-based carriers, inclusion complexes, micelles, and conjugate-based delivery systems are all examples of approaches that can deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery system to carry quercetin molecules to senescent cells in order to destroy them [1]. They created magnetite nanoparticles and coated their surface with quercetin molecules, then examined the senolytic action of this approach.
They found that the nanoparticles were effective at attenuating inflammatory signals, such as interleukin 8 and interferon beta, which are secreted by senescent cells. They also found that cells forced into early senescence via stress were destroyed by the nanoparticles and that the secretion of inflammatory signals was reduced.Doing this also led to an elevated activity of AMP-activated protein kinase (AMPK). This is a critical nutrient and energy sensing enzyme that is present in all mammalian cells and maintains energy homeostasis. When activated, it facilitates energy-generating processes, such as glucose uptake and fatty acid oxidation, and decreases energy-consuming processes, such as protein and lipid synthesis. AMPK is one of the four pathways that control our metabolism, and its deregulation is a proposed reason why we age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging.
Senescent cells only make up a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging and cancer; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that often has poor water solubility, chemical instability, or poor bioavailability. These confounding factors could be muddling its effectiveness and making it unreliable as a senolytic therapy. This likely explains why different senolytic studies using quercetin have yielded conflicting results: there are simply too many processes that can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials that quercetin, when used in combination with the cancer drug dasatinib, can be the basis for an effective therapy for eliminating senescent cells. Unfortunately, on its own, quercetin does not have a significant senolytic effect, which is possibly due to its limitations as a polyphenol.
However, there are ways to overcome these issues with quercetin and other similar polyphenols, and that is by using special delivery systems that make the molecules more effective and controllable. Polymer nanoparticles, lipid-based carriers, inclusion complexes, micelles, and conjugate-based delivery systems are all examples of approaches that can deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery system to carry quercetin molecules to senescent cells in order to destroy them [1]. They created magnetite nanoparticles and coated their surface with quercetin molecules, then examined the senolytic action of this approach.
They found that the nanoparticles were effective at attenuating inflammatory signals, such as interleukin 8 and interferon beta, which are secreted by senescent cells. They also found that cells forced into early senescence via stress were destroyed by the nanoparticles and that the secretion of inflammatory signals was reduced.Doing this also led to an elevated activity of AMP-activated protein kinase (AMPK). This is a critical nutrient and energy sensing enzyme that is present in all mammalian cells and maintains energy homeostasis. When activated, it facilitates energy-generating processes, such as glucose uptake and fatty acid oxidation, and decreases energy-consuming processes, such as protein and lipid synthesis. AMPK is one of the four pathways that control our metabolism, and its deregulation is a proposed reason why we age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.
NAD+ availability decreases with age and in certain disease conditions.
Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been
shown to enhance NAD+ biosynthesis and ameliorate various pathologies in
mouse disease models. In this study, we conducted a 12-month-long NMN
administration to regular chow-fed wild-type C57BL/6N mice during their
normal aging. Orally administered NMN was quickly utilized to synthesize
NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated
physiological decline in mice. Without any obvious toxicity or
deleterious effects, NMN suppressed age-associated body weight gain,
enhanced energy metabolism, promoted physical activity, improved insulin
sensitivity and plasma lipid profile, and ameliorated eye function and
other pathophysiologies. Consistent with these phenotypes, NMN prevented
age-associated gene expression changes in key metabolic organs and
enhanced mitochondrial oxidative metabolism and mitonuclear protein
imbalance in skeletal muscle. These effects of NMN highlight the
preventive and therapeutic potential of NAD+ intermediates as effective
anti-aging interventions in humans.wisepoqder beta-Nicotinamide mononucleotide powder
Historically unprecedented worldwide trends in population aging are predicted to become an incessant burden on governmental healthcare finances (OECD, 2013). To make the process of aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016, Hubbard and Sinclair, 2014, Lamming et al., 2013). Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010, Imai and Guarente, 2014).
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), key NAD+ intermediates in mammals, could be such candidates (Imai, 2010). NMN is synthesized from nicotinamide (Nic), an amide form of vitamin B3, and 5′-phosphoribosyl-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this particular NAD+ biosynthetic pathway (Cantó et al., 2015, Imai and Guarente, 2014). NR is phosphorylated to NMN by nicotinamide riboside kinases (NRKs) (Belenky et al., 2007). Once NMN is synthesized, it is converted to NAD+ by three NMN adenylyltransferases, NMNAT1-3. The short-term administration of either NMN or NR has been reported to have remarkable therapeutic effects on metabolic complications and other disease conditions. For example, we have shown that NMN ameliorates impairments in glucose-stimulated insulin secretion in aged wild-type mice and some genetic mouse models (Ramsey et al., 2008, Revollo et al., 2007). NMN treatment also significantly improves both insulin action and secretion in diet- and age-induced type 2 diabetic or obese mouse models (Caton et al., 2011, Yoshino et al., 2011). Furthermore, NMN protects the heart from ischemia/reperfusion injury by preventing NAD+ decrease induced by ischemia (Yamamoto et al., 2014), maintains the neural stem/progenitor cell population, and restores skeletal muscle mitochondrial function and arterial function in aged mice (de Picciotto et al., 2016, Gomes et al., 2013, Stein and Imai, 2014), ameliorates mitochondrial function, neural death, and cognitive function in Alzheimer’s disease rodent models (Long et al., 2015, Wang et al., 2016). NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012, Gariani et al., 2015, Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014, Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s disease model mice (Gong et al., 2013), prevent DNA damage and hepatocellular carcinoma formation (Tummala et al., 2014), improve noise-induced hearing loss (Brown et al., 2014), and maintain muscle stem cell function (Zhang et al., 2016). Collectively, these findings strongly suggest that enhancing NAD+ biosynthesis by administering NMN or NR is an efficient therapeutic intervention against many disease conditions (Imai and Guarente, 2014).
Interestingly, it has been demonstrated that enhancing NAD+ biosynthesis extends lifespan in yeast, worms, and flies (Anderson et al., 2002, Balan et al., 2008, Mouchiroud et al., 2013). In rodents and humans, a number of studies have reported that NAD+ content declines with age in multiple organs, such as pancreas, adipose tissue, skeletal muscle, liver, skin, and brain (Gomes et al., 2013, Massudi et al., 2012, Mouchiroud et al., 2013, Stein and Imai, 2014, Yoshino et al., 2011, Zhu et al., 2015). Thus, enhancing NAD+ biosynthesis with NMN or NR is expected to provide significant preventive effects on various pathophysiological changes in the natural process of aging. To address this critical question, long-term administration studies need to be performed under normal conditions in wild-type mice.
To examine whether long-term administration of NMN shows preventive effects on age-associated pathophysiological changes, we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water. We assessed a variety of functional traits, as well as long-term safety and toxicity, and found that NMN is remarkably capable of ameliorating age-associated physiological decline in mice. Our findings from this long-term administration study provide a proof of concept to develop NMN as an effective anti-aging compound that prevents age-associated physiological decline, hoping to translate the results to humans.
Historically unprecedented worldwide trends in population aging are predicted to become an incessant burden on governmental healthcare finances (OECD, 2013). To make the process of aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016, Hubbard and Sinclair, 2014, Lamming et al., 2013). Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010, Imai and Guarente, 2014).
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), key NAD+ intermediates in mammals, could be such candidates (Imai, 2010). NMN is synthesized from nicotinamide (Nic), an amide form of vitamin B3, and 5′-phosphoribosyl-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this particular NAD+ biosynthetic pathway (Cantó et al., 2015, Imai and Guarente, 2014). NR is phosphorylated to NMN by nicotinamide riboside kinases (NRKs) (Belenky et al., 2007). Once NMN is synthesized, it is converted to NAD+ by three NMN adenylyltransferases, NMNAT1-3. The short-term administration of either NMN or NR has been reported to have remarkable therapeutic effects on metabolic complications and other disease conditions. For example, we have shown that NMN ameliorates impairments in glucose-stimulated insulin secretion in aged wild-type mice and some genetic mouse models (Ramsey et al., 2008, Revollo et al., 2007). NMN treatment also significantly improves both insulin action and secretion in diet- and age-induced type 2 diabetic or obese mouse models (Caton et al., 2011, Yoshino et al., 2011). Furthermore, NMN protects the heart from ischemia/reperfusion injury by preventing NAD+ decrease induced by ischemia (Yamamoto et al., 2014), maintains the neural stem/progenitor cell population, and restores skeletal muscle mitochondrial function and arterial function in aged mice (de Picciotto et al., 2016, Gomes et al., 2013, Stein and Imai, 2014), ameliorates mitochondrial function, neural death, and cognitive function in Alzheimer’s disease rodent models (Long et al., 2015, Wang et al., 2016). NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012, Gariani et al., 2015, Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014, Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s disease model mice (Gong et al., 2013), prevent DNA damage and hepatocellular carcinoma formation (Tummala et al., 2014), improve noise-induced hearing loss (Brown et al., 2014), and maintain muscle stem cell function (Zhang et al., 2016). Collectively, these findings strongly suggest that enhancing NAD+ biosynthesis by administering NMN or NR is an efficient therapeutic intervention against many disease conditions (Imai and Guarente, 2014).
Interestingly, it has been demonstrated that enhancing NAD+ biosynthesis extends lifespan in yeast, worms, and flies (Anderson et al., 2002, Balan et al., 2008, Mouchiroud et al., 2013). In rodents and humans, a number of studies have reported that NAD+ content declines with age in multiple organs, such as pancreas, adipose tissue, skeletal muscle, liver, skin, and brain (Gomes et al., 2013, Massudi et al., 2012, Mouchiroud et al., 2013, Stein and Imai, 2014, Yoshino et al., 2011, Zhu et al., 2015). Thus, enhancing NAD+ biosynthesis with NMN or NR is expected to provide significant preventive effects on various pathophysiological changes in the natural process of aging. To address this critical question, long-term administration studies need to be performed under normal conditions in wild-type mice.
To examine whether long-term administration of NMN shows preventive effects on age-associated pathophysiological changes, we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water. We assessed a variety of functional traits, as well as long-term safety and toxicity, and found that NMN is remarkably capable of ameliorating age-associated physiological decline in mice. Our findings from this long-term administration study provide a proof of concept to develop NMN as an effective anti-aging compound that prevents age-associated physiological decline, hoping to translate the results to humans.
Pyrroloquinoline Quinone (PQQ) is a unique micro-nutrient; a
vitamin-like compound found naturally in plant foods and green tea. PQQ
has been shown to provide a wide range of benefits to brain and body
function based upon clinical evaluations. PQQ has been researched and
studied closely for over 30 years.wisepoqder Pyrroloquinoline quinone
PQQ is a powerful anti-oxidant capable of catalyzing repeated oxidation and reduction reactions to a much greater degree compared to other anti-oxidants. PQQ promotes the generation of new mitochondria within aging cells, called mitochondrial biogenesis, and improves mitochondrial function; a “fountain of youth” effect”. This support of mitochondrial growth improves energy production.
PQQ has tremendous potential to help with neurological conditions that revolve around low mitochondrial function and can support the body’s efforts to combat against the loss of memory and cognitive skills, as the body ages.
TAKING PQQ
If you want to add a PQQ supplement to your diet, it’s important to remember that a little goes a long way. Since it doesn’t take much PQQ to have an effect, most dosages are kept small. As a result, most people don’t have to worry about any PQQ side effects.
PQQ is a very effective nootropic that everyone should include in their stack of choice. It may provide you with more energy, improved sleep, and an enhanced memory in addition to some possible other benefits. There’s a lot to be gained from taking PQQ.
PQQ is a powerful anti-oxidant capable of catalyzing repeated oxidation and reduction reactions to a much greater degree compared to other anti-oxidants. PQQ promotes the generation of new mitochondria within aging cells, called mitochondrial biogenesis, and improves mitochondrial function; a “fountain of youth” effect”. This support of mitochondrial growth improves energy production.
PQQ has tremendous potential to help with neurological conditions that revolve around low mitochondrial function and can support the body’s efforts to combat against the loss of memory and cognitive skills, as the body ages.
TAKING PQQ
If you want to add a PQQ supplement to your diet, it’s important to remember that a little goes a long way. Since it doesn’t take much PQQ to have an effect, most dosages are kept small. As a result, most people don’t have to worry about any PQQ side effects.
PQQ is a very effective nootropic that everyone should include in their stack of choice. It may provide you with more energy, improved sleep, and an enhanced memory in addition to some possible other benefits. There’s a lot to be gained from taking PQQ.
Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in
various foods and mammalian tissues, has received an increasing amount
of attention because of a number of health benefits that can be
attributed to its ability to enhance mitochondrial biogenesis. However,
its underlying molecular mechanism remains incompletely understood. We
have now established that the exposure of mouse NIH/3T3 fibroblasts to a
physiologically relevant concentration of PQQ significantly stimulates
mitochondrial biogenesis.
The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). wisepoqder Pyrroloquinoline quinone powder
Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). wisepoqder Pyrroloquinoline quinone powder
Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
Kylie’s been busy extending her make-up empire and fans have seen her
pushing her latest venture, Kylie Skin, across social media. We’ve had
promo videos, fresh-faced selfies and that 10-second face wash tutorial
that even Kim Kardashion poked fun of – but, anything Kylie can do, Will
can do better. The Aladdin star took to Instagram with his own ‘beauty
tips’ and ‘beauty secrets’, giving the Keeping Up With The Kardashians
star a run for her money and we loved every second.atasi jerawat
Will plays Genie in the live action re-make of the Disney movie and decided to film a little something to reveal the key to his ‘Genie magic’. Eyeliner – in case you were wondering. And a good face mask. Posting his spoof tutorial to Instagram, Will is sat in his dressing room and says: ‘The big part I hate about not being able to play Genie is eyeliner. I really like wearing eyeliner. ‘You see how pretty my eyes are?’ Next, he moves on to that Genie glow and applies a mask with a face exfoliator. We told you, he’s dedicated.
I don’t want Kylie Jenner stealing my stuff,’ he joked while layering on the ‘brown stuff’. If the Kylie dig wasn’t enough to have you in stitches, then Will’s demonstration will. ‘The brown stuff has nature in it,’ he says while going to town with the exfoliator. ‘It goes in a circular motion and you go in a circular motion and you’ve always got to keep the battery low, so it barely works.’ Totally deadpan, he then goes: ‘Oh, and you’ve got to be careful because it makes your skin black… and that’s why my skin looks so good.’
Him throwing shade at Kylie comes after he and his wife Jada Pinkett Smith were on hand to support her former BFF Jordyn Woods when the whole Tristan Thompson scandal broke. Jordyn has been tight with Will and Jada ever since she was little and Jada gave her the platform to set the record straight on what really happened with Tristan on her talk show Red Table Talk.
Jordyn and Tristan were caught cheating at a house party in LA, but the model insisted they never slept together – Tristan had kissed her goodbye when she left the party. It was enough for Khloe Kardashian to dump her baby daddy Tristan, ending their three year relationship. Kylie has reportedly cut ties with Jordyn – washing her hands off their long-term friendship just like she did her face.
Will plays Genie in the live action re-make of the Disney movie and decided to film a little something to reveal the key to his ‘Genie magic’. Eyeliner – in case you were wondering. And a good face mask. Posting his spoof tutorial to Instagram, Will is sat in his dressing room and says: ‘The big part I hate about not being able to play Genie is eyeliner. I really like wearing eyeliner. ‘You see how pretty my eyes are?’ Next, he moves on to that Genie glow and applies a mask with a face exfoliator. We told you, he’s dedicated.
I don’t want Kylie Jenner stealing my stuff,’ he joked while layering on the ‘brown stuff’. If the Kylie dig wasn’t enough to have you in stitches, then Will’s demonstration will. ‘The brown stuff has nature in it,’ he says while going to town with the exfoliator. ‘It goes in a circular motion and you go in a circular motion and you’ve always got to keep the battery low, so it barely works.’ Totally deadpan, he then goes: ‘Oh, and you’ve got to be careful because it makes your skin black… and that’s why my skin looks so good.’
Him throwing shade at Kylie comes after he and his wife Jada Pinkett Smith were on hand to support her former BFF Jordyn Woods when the whole Tristan Thompson scandal broke. Jordyn has been tight with Will and Jada ever since she was little and Jada gave her the platform to set the record straight on what really happened with Tristan on her talk show Red Table Talk.
Jordyn and Tristan were caught cheating at a house party in LA, but the model insisted they never slept together – Tristan had kissed her goodbye when she left the party. It was enough for Khloe Kardashian to dump her baby daddy Tristan, ending their three year relationship. Kylie has reportedly cut ties with Jordyn – washing her hands off their long-term friendship just like she did her face.
Millie Bobby Brown has responded to accusations that she oddly “didn't
apply anything” to her face in new video highlighting products from her
clean beauty line, Florence by Mills.
In recent days, the "Stranger Things" star shared her “nighttime skin routine” with the cosmetics on social media, but many viewers agreed that it didn’t look like she was doing anything to her face at all.angkat komedo
In the nearly two-minute clip, which has since been deleted from Instagram but remains on YouTube, Brown demonstrates a face mist, a scrub, a facewash, a moisturizer, and lip oil, claiming to have washed off her face between at least two of the steps.But, as some pointed out, the 15-year-old actress appears to retain her eye makeup throughout, leading some to believe she was just pretending to use the products and rubbing her dry hands all over her face.
“The mist is the only thing she actually used!” on YouTube commenter complained. “This girl basically just spent two minutes rubbing her face with her bare hands.”
“Wow, a magic invisible product that we couldn't even see being applied,” another smirked. “Millie is such a great actress.”I am so confused… if she was actually applying something then all her makeup would be smudging and coming off,” one added.
On Sept. 12, Brown took the makeup matter into her own hands and responded to the accusations on Instagram with a new post.“I'm still learning the best way to share my routines as I get to know this space better – I'm not an expert,” the “Godzilla” star admitted. “I thought doing a quick video replicating my personal process that night was okay, but that's not what was conveyed. I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too!”
In recent days, the "Stranger Things" star shared her “nighttime skin routine” with the cosmetics on social media, but many viewers agreed that it didn’t look like she was doing anything to her face at all.angkat komedo
In the nearly two-minute clip, which has since been deleted from Instagram but remains on YouTube, Brown demonstrates a face mist, a scrub, a facewash, a moisturizer, and lip oil, claiming to have washed off her face between at least two of the steps.But, as some pointed out, the 15-year-old actress appears to retain her eye makeup throughout, leading some to believe she was just pretending to use the products and rubbing her dry hands all over her face.
“The mist is the only thing she actually used!” on YouTube commenter complained. “This girl basically just spent two minutes rubbing her face with her bare hands.”
“Wow, a magic invisible product that we couldn't even see being applied,” another smirked. “Millie is such a great actress.”I am so confused… if she was actually applying something then all her makeup would be smudging and coming off,” one added.
On Sept. 12, Brown took the makeup matter into her own hands and responded to the accusations on Instagram with a new post.“I'm still learning the best way to share my routines as I get to know this space better – I'm not an expert,” the “Godzilla” star admitted. “I thought doing a quick video replicating my personal process that night was okay, but that's not what was conveyed. I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too!”
The Stranger Things star took to Instagram on Thursday to address the
criticism she received over a nighttime skincare routine tutorial.
"I'm still learning the best way to share my routines as I get to know this space better—I'm not an expert," she wrote in a note posted to the social network. "I thought doing a quick video replicating my personal process for that night was okay, but that's not what was conveyed. I understand, I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too. Ily guys x #LovedAndLight."Tutorial makeup
The 15-year-old actress posted the tutorial on YouTube last weekend. In the one-minute and 50-second clip, the celebrity talked about the products from her Florence by Mills line and walked viewers through a routine, which included using a face mist, a scrub, a face wash, a moisturizer and a lip oil.However, viewers had some serious questions about the video—mainly over if she actually used the products. For instance, some wondered why her hair was still dry and why her makeup was still intact after allegedly washing her face.
"You know how when you actually wash your face with water your hair gets a little bit wet or damp around the face? She kept saying she was washing the soap off, but her hair was perfectly dry at all times," one YouTube commenter wrote. "I would have expected to see a little remnant of the rinsing process at least since she rinsed at least twice over. And the [mist] kinda didn't get on her face. This was weird. The eye makeup was still on."
Others questioned the sporadic cuts throughout the video, which usually took place right after she said she was going to "wash off." Some even accused the celebrity of using empty bottles.
"I'm still learning the best way to share my routines as I get to know this space better—I'm not an expert," she wrote in a note posted to the social network. "I thought doing a quick video replicating my personal process for that night was okay, but that's not what was conveyed. I understand, I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too. Ily guys x #LovedAndLight."Tutorial makeup
The 15-year-old actress posted the tutorial on YouTube last weekend. In the one-minute and 50-second clip, the celebrity talked about the products from her Florence by Mills line and walked viewers through a routine, which included using a face mist, a scrub, a face wash, a moisturizer and a lip oil.However, viewers had some serious questions about the video—mainly over if she actually used the products. For instance, some wondered why her hair was still dry and why her makeup was still intact after allegedly washing her face.
"You know how when you actually wash your face with water your hair gets a little bit wet or damp around the face? She kept saying she was washing the soap off, but her hair was perfectly dry at all times," one YouTube commenter wrote. "I would have expected to see a little remnant of the rinsing process at least since she rinsed at least twice over. And the [mist] kinda didn't get on her face. This was weird. The eye makeup was still on."
Others questioned the sporadic cuts throughout the video, which usually took place right after she said she was going to "wash off." Some even accused the celebrity of using empty bottles.