Light therapy has been studied through intensive scientific research over the past 40 years, specifically under an area known as low level laser therapy, or nowadays referred to as photobiomodulation. It is understood that the targeted wavelength of the red light spectrum, to nm, can penetrate the skin millimeters, working from the inside-out to enhance mitochondrial function and thus benefit the skin.

It has been noted in research that nm wavelength is closest to the resonant frequency of cell tissue and can subsequently be absorbed better in the hemoglobin, the carrier of oxygen in red blood cells. Near-infrared NIR wavelengths that function at the or nm level have been shown to penetrate far deeper beneath the skin to tissue and bone.

Based on research at NASA, NIR emitted through color specific LED bulbs operate by activating color sensitive chemicals in body tissues. The combination of red light, which offers healing to the skin, and NIR, as healing to deeper organs, means a light therapy that improves our energy and healing, upgrades our health, enhances how the brain works because its energy workload is freed up and it can achieve higher grade energy production.

Research study programs reveal health benefits that include enhanced blood circulation, anti-inflammatory effects, increased muscle recovery, improved skin tone and glow, reduced wrinkles and scars, improved wound healing, pain reduction, lymphatic flow boost, increased cellular growth, and even enhanced fertility and increased testosterone.

A reduction of inflammation on both the skin and inner organs improves health and aids the reduction of inflammation in the brain to improve brain function. Take any opportunity you have to spend time outside in good, natural light. This is especially beneficial at the start of the day.

One of the best ways to handle jet lag is to get up at dawn on your first wake up day in your new time zone and be outside, under the light looking towards the sun, whether cloudy or clear skies.

Also take any opportunity to walk to work, school or the stores, and sit outside for lunch. The environment of Samahita is a natural light and fresh air paradise. This is one of the reasons you can leave feeling better as it enhances all the other life-giving health practices you do here.

We also go a few steps further to enhance your brain wellness in our Brain Health Upgrade program. One of the therapies in this program involves mitochondria enhancing red and NIR light therapy.

Improved cellular functioning and energy production helps your brain, similar to providing a cleaner more efficient energy supply to your car or house. The focus of this program is to improve the production of that energy supply, enhance its delivery, and optimize its use, for and within the brain.

The challenges of the modern world cannot allow us to take for granted that our brain is just going to perform well. The statistics show the shocking rise of dementia and related mental pathologies with the unfortunate reality of modern life being further removed from nature and her glorious inputs.

Yoga, meditation and upgraded actions are not just needed, they are unavoidably essential today. As a result, Paul occupies a unique space to impart genuine teaching and science on the breath, body, and meditative practices, seen as a Teacher-of-teachers and identified to carry on the tradition of Pranayama.

His sincere and ongoing role is to teach, write and research, to help put out experienced and authentic information on these areas of how we live, breathe and be, to help people improve their mental and physical health, and live more fulfilling lives.

For more on his background see his bio. This site uses cookies. By continuing to browse the site, you are agreeing to our use of cookies. Not only can this affect the way we feel and leave us struggling with fatigue, but it also means there is less energy available for repair and rejuvenation.

Another common effect of mitochondrial dysfunction is loss of muscle strength, which many people begin to experience during their 40s due to the age-related decline in both the number and function of mitochondria.

Supplements, such as urolithin A , can be used to boost mitochondrial health and energy production. Your gut plays a key role in this process as urolithin A, which is a powerful postbiotic, is produced by the gut bacteria after eating certain foods high in polyphenols like pomegranates, berries and nuts.

However, the supplement story is not that straightforward; recent research has shown that it is difficult for most people to produce any or enough urolithin A from food alone — in fact, as few as 1 in 3 people are able to produce enough urolithin A, and that is still subject to their eating enough of the right foods at the right time.

The most effective way to ensure you are getting enough urolithin A is from direct supplementation. This is where Mitopure comes in. Swiss company Amazentis has developed a highly-purified form of urolithin A called Mitopure which you can buy as powder or softgels. Containing mg of highly-pure urolithin A, Mitopure packs an energy punch, delivering six times the amount of urolithin A than diet alone and has been shown to promote both mitochondrial health and muscle endurance.

Taking the supplements for two months can improve markers of muscular strength in older adults, without any exercise. By supporting mitochondrial health, urolithin A is also thought to boost longevity by benefiting numerous age-related diseases. It does this by improving the activity of mitochondria and increasing muscle function.

By activating mitophagy, the selective recycling of aging and damaged mitochondria, the path is cleared for healthy mitochondria to grow and fight the battle against aging.

READ MORE: Are you getting enough urolithin A? Why superfoods may not be the answer to longevity. The information included in this article is for informational purposes only.

The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. Cell Biol. Cunnane, S. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.

Drug Discov. Dang, W. Histone H4 lysine 16 acetylation regulates cellular lifespan. Ding, S. Inhibiting MicroRNAa protects myocardial ischemia-reperfusion injury by targeting SIRT1 and suppressing oxidative stress and NLRP3-mediated pyroptosis pathway. Dominy, J. Acta , — Dong, X.

Sirtuin biology and relevance to diabetes treatment. Diabetes Manag. Dong, W. Aβ25—35 suppresses mitochondrial biogenesis in primary hippocampal neurons. Dorling, J. Calorie restriction for enhanced longevity: the role of novel dietary strategies in the present obesogenic environment.

Ageing Res. Espada, L. Loss of metabolic plasticity underlies metformin toxicity in aged Caenorhabditis elegans. Fang, E. Cell , — Feng, X. Berberine in cardiovascular and metabolic diseases: from mechanisms to therapeutics. Theranostics 9, — Gao, Z. Sirtuin 1 SIRT1 protein degradation in response to persistent c-Jun N-terminal kinase 1 JNK1 activation contributes to hepatic steatosis in obesity.

Gao, Y. Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy. Redox Biol. Ge, X. Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR and modulating SIRT1 expression.

Aging 11, — Gerhart-Hines, Z. Cell 44, — Gomes, A. Gong, C. ILinduced acetylation of E2F1 aggravates oxidative damage of retinal pigment epithelial cell line. Eye Res. Guo, Q. Tumor necrosis factor-α TNF-α enhances miRmediated endothelial senescence by targeting sirtuin1 SIRT1.

Gurd, B. High-intensity interval training increases SIRT1 activity in human skeletal muscle. Han, L. SIRT1 is regulated by a PPARγ-SIRT1 negative feedback loop associated with senescence.

Nucleic Acids Res. Hayashida, S. Herzig, S. AMPK: guardian of metabolism and mitochondrial homeostasis. Hikosaka, K. Implications of NAD metabolism in pathophysiology and therapeutics for neurodegenerative diseases. Hong, Y. The role of sirtuins in kidney diseases. Hu, M. SRC-3 is involved in maintaining hematopoietic stem cell quiescence by regulation of mitochondrial metabolism in mice.

Blood , — Hu, C. Huang, Q. A SIRT1 activator, ginsenoside Rc, promotes energy metabolism in cardiomyocytes and neurons. Huber, J. SIRT1-independent mechanisms of the putative sirtuin enzyme activators SRT and SRT Future Med.

Ji, M. Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Jiang, M. Jiao, F. The beneficial roles of SIRT1 in neuroinflammation-related diseases. Joshi, A. Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration.

Juszczak, F. Critical role for AMPK in metabolic disease-induced chronic kidney disease. Karstoft, K. Resting metabolic rate does not change in response to different types of training in subjects with type 2 diabetes. Kerr, J. Trends Neurosci. Knuiman, P. Select skeletal muscle mRNAs related to exercise adaptation are minimally affected by different pre-exercise meals that differ in macronutrient profile.

Kosgei, V. Sirt1-PPARS cross-talk in complex metabolic diseases and inherited disorders of the one carbon metabolism. Cells Koves, T. Peroxisome proliferator-activated receptor-γ co-activator 1α-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency.

Lamb, D. Aging 12, — Lamichane, S. MHY attenuates replicative cellular senescence in human endothelial progenitor cells SIRT1 signaling. Lan, Y. SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging.

Nucleic Acids 23, — Lan, F. Resveratrol-induced AMP-activated protein kinase activation is cell-type dependent: lessons from basic research for clinical application. Nutrients Li, T. Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation. Cancer Res. Li, X. SIRT1 activation promotes angiogenesis in diabetic wounds by protecting endothelial cells against oxidative stress.

Li, H. Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. Li, Z. Resveratrol promotes white adipocytes browning and improves metabolic disorders in Sirt1-dependent manner in mice.

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Phosphorylation regulates SIRT1 function. PLoS One 3:e Scheibye-Knudsen, M. Contribution of defective mitophagy to the neurodegeneration in DNA repair-deficient disorders. Autophagy 10, — Schöndorf, D. Cell Rep. Shan, Y. Adipose tissue SIRT1 regulates insulin sensitizing and anti-inflammatory effects of berberine.

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Moderate doses of resveratrol 25 μM can stimulate AMPK in vitro and in vivo through the SIRT1-dependent pathway, resulting in more sustained improvement of mitochondrial function.

On the contrary, a high dose of resveratrol 50μM not only leads to the activation of AMPK in a SIRT1-independent manner, but also leads to a significant reduction in mitochondrial function and intracellular ATP level Price et al.

If the dose of resveratrol has a significant effect on the results, then the low bioavailability of resveratrol itself in humans is also one of the problems that researchers urgently need to solve.

Given the rapid metabolism of resveratrol in the liver and the influence of intestinal microflora in the intestine, researchers have developed a series of drug delivery systems such as embedding resveratrol in lipid nanoparticles or liposomes, using emulsions or micelles.

Resveratrol derivatives such as SRT have also been developed, and preparations such as resVida and Longivinex that can greatly improve the bioavailability of resveratrol have been designed Chimento et al.

Currently, the direction of searching for STAC is mainly extracted from natural products or artificially designed compounds according to the structure of SIRT1. In the latest screening, scientists found 19 kinds of STAC with anti-mitochondrial oxidative damage from traditional medicinal plants.

Further studies on several of these activators have found that these compounds including ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A can enhance SIRT1 deacetylation activity, promote mitochondrial functional recovery by restoring oxygen consumption and increasing mitochondrial biogenesis, increase ATP production, decrease intracellular ROS levels, and strengthen antioxidant mechanisms Wang et al.

Ginsenoside is the main active component of the pharmacological activity of Panax ginseng. Ginsenosides are classified according to different structural types, recent studies found that ginsenoside Rg3 can enhance the endurance of aged rats during exercise by affecting the activity of SIRT1 and the expression of PGC-1α Yang et al.

Consistent with this, as a STAC, ginsenoside Rc can promote energy metabolism in cardiomyocytes and neurons by activating the SIRT1-PGC-1α pathway to induce mitochondrial biosynthesis Huang et al.

SRT is a small molecular activator that is structurally independent of resveratrol, but its activation effect is hundreds of times that of resveratrol. It has the same effect as SRT and resveratrol and effectively solves the weakness of the low bioavailability of resveratrol.

Resveratrol and SRT bind at the same molecular site to activate SIRT1 activity and play a similar role in regulating the stability between mitochondrial biogenesis and mitochondrial autophagy. Activation of SIRT1 by SRT increased mitochondrial biosynthesis via PGC-1α-dependent pathways, promoted the recovery of mitochondrial protein and function, and induced the protective effect of brain injury after intracerebral hemorrhage in rats Zhou et al.

SRT can produce neuroprotective effects similar to resveratrol, reduce the content of Aβ in the brain of PD patients, and repair the autophagy dysfunction Bai et al. Studies have also shown that SRT plays an active role in the treatment of diabetes and insulin resistance, SRT can promote wound healing and angiogenesis in diabetic mice in vivo and in vitro by activating SIRT1 Li et al.

However, studies have shown that the metabolic role of SRT depends on AMPK, which is because SRT cannot promote mitochondrial function and improve glucose tolerance in AMPKα 2 knockout mice Park et al.

At present, several other STACs: such as SRT, SRT, RT, SRT, and CAY, have been developed Figure 2 , although there are few related studies, preliminary experiments have shown that they activate SIRT1 to mimic the anti-aging effects of resveratrol and improve the metabolic function of diabetic type 2 diabetes and obese mice Zhang et al.

Based on this effect, new drug strategies can be provided for the treatment of metabolic disorders and age-related diseases. However, some scholars have put forward their views on the mechanism of STAC.

They reported that SRT and SRT can effectively reduce acetylated p53 in cells treated with DNA damage agents by inhibiting the activity of P histone acetyltransferase even in cells lacking SIRT1 Huber et al. Recently, scholars have revealed the epigenetic alterations in patients with AD through an integrated multi-omics approach, in which the up-regulation of histone acetyltransferase expression in H3K27ac and H3K9ac leads to an increase in their acetylation level, and the activity and expression of SIRT1 in AD patients are also decreased Nativio et al.

Part of the mechanism of metformin in the anti-aging and treatment of type 2 diabetes and neurodegenerative diseases is achieved by stimulating AMPK.

The researchers found that AMPK activated by metformin preconditioning can effectively reduce the disorder of glucose and lipid metabolism, cellular oxidative stress, and renal function damage in diabetic rats through the SIRT1-dependent pathway, which has a protective effect on the pathological process of diabetes and diabetic nephropathy Ren et al.

In addition, the effects of metformin vary by cell and age. Metformin can activate AMPK and its downstream signal pathways in neurocytes, promote the recovery of mitochondrial function and reduce the accumulation of toxic proteins.

Metformin combination therapy can even restore broken mitochondria to an almost normal state, thus meeting the energy needs of cells and improving age-related neurodegenerative diseases Sharma et al. Contrary to the anti-aging effect observed in young nematodes, metformin can aggravate aging-related mitochondrial dysfunction and lead to a shortening of life span in old Caenorhabditis elegans Espada et al.

Metformin plays a beneficial role by activating SIRT1-mediated, AMPK-independent autophagy pathways, and also combats the inhibition of intracytoplasmic P53 on parkin-mediated mitophagy, thus maintain mitochondrial quality Song et al. This result is similar to another study, metformin promotes the expression of mitophagy-related genes to restore parkin-mediated mitophagy pathway activity, maintain mitochondrial integrity and cell survival, protect cells from high glucose-induced damage Zhao and Sun, However, the association between mitophagy and SIRT1 has not been fully elucidated.

Moreover, the tricyclopyranone compound CP2 Zhang et al. The imbalance of energy supply and demand make the body in a state of energy stress. Cells often redistribute the energy generated to important mechanisms and activities when the energy supply cannot meet the energy demand.

As the main energy producer, the energy production of mitochondria is closely regulated by a variety of energy receptors in cells. Promoting the biosynthesis and function of mitochondria to produce enough ATP to meet the energy gap of cells has become an important means to break the energy stress state of cells.

However, the expression and activity of SIRT1 decreased significantly in pathological conditions such as aging or age-related diseases. In this review, we discussed that precise regulation of SIRT1 activity at all levels can eliminate cellular energy stress. We also discussed that SIRT1 molecular activator can promote the activity and expression of SIRT1 and play a useful role, which can be used as promising methods for the treatment of aging, neurodegenerative diseases, metabolic diseases, and other diseases.

Other studies also have found that a long-term CR diet can improve metabolism and promote fat loss, but the effect of fat loss will be quickly reversed once stopped Melo et al. Therefore, I think we can implement CR with a continuous and progressive degree on mice to observe the effect on the body compared with the effect of CR with a constant degree of persistence.

At the same time, the effect on weight reversal was observed by progressively reducing the extent of the CR diet rather than abruptly stopping the CR diet at the end. On the other hand, our study found that mitochondrial function is impaired under pathological conditions, which may be partly due to changes in mitochondrial dynamics and increased mitochondrial fragmentation Yang D.

The SIRT1 pathway is beneficial to restore the quality and efficiency of mitochondria, so promoting the dynamic recovery of mitochondria is expected to be achieved by promoting the biosynthesis of mitochondria. Previous studies mainly focused on the nuclear-cytoplasmic shuttle of SIRT1.

The subcellular localization of SIRT1 shows that SIRT1 in mitochondria can also communicate with SIRT1 in the cytoplasm, which provides a basis for us to accurately regulate the function of mitochondria through SIRT1.

In conclusion, although the mechanisms of SIRT1 and SIRT1-related activators in anti-aging and age-related diseases have not been clarified in detail, there is a complex and inseparable relationship between the fine regulation mechanism of SIRT1 activity and expression and the mitochondria function.

Therefore, it is extremely important to further clarify the causal relationship between them to provide direction for the promotion of human health and anti-aging. YF, JY and FH: conception, designing, and writing of the manuscript. XW, JY, DY, WY, XL and QZ: assisted in literature search, conception, and writing of the manuscript.

FH, YL and GW: conception and revising the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by grants from the National Natural Science Foundation of China and , Natural Science Foundation of Jiangxi Province BCB and BABL , and Youth Team Project of the Second Affiliated Hospital of Nanchang University YNTD The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

We apologize in advance to those researchers who contributed to the field and their publications were not listed in this review. Bai, L. Attenuation of Pb-induced Aβ generation and autophagic dysfunction via activation of SIRT1: neuroprotective properties of resveratrol. doi: PubMed Abstract CrossRef Full Text Google Scholar.

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Alzheimers Dis. Chandrasekaran, K. Cheang, W. Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor δ.

Chelladurai, P. Targeting histone acetylation in pulmonary hypertension and right ventricular hypertrophy. Chen, P. Neurotherapeutics 16, — Cheng, Z. Neuroprotective effects of ginsenosides against cerebral ischemia. Molecules Chimento, A. Progress to improve oral bioavailability and beneficial effects of resveratrol.

Chini, C. Choi, S. Obesity-linked phosphorylation of SIRT1 by casein kinase 2 inhibits its nuclear localization and promotes fatty liver.

Corpas, R. Resveratrol induces brain resilience against alzheimer neurodegeneration through proteostasis enhancement. Covarrubias, A. Cell Biol. Cunnane, S. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.

Drug Discov. Dang, W. Histone H4 lysine 16 acetylation regulates cellular lifespan. Ding, S. Inhibiting MicroRNAa protects myocardial ischemia-reperfusion injury by targeting SIRT1 and suppressing oxidative stress and NLRP3-mediated pyroptosis pathway. Dominy, J.

Acta , — Dong, X. Sirtuin biology and relevance to diabetes treatment. Diabetes Manag. Dong, W. Aβ25—35 suppresses mitochondrial biogenesis in primary hippocampal neurons. Dorling, J. Calorie restriction for enhanced longevity: the role of novel dietary strategies in the present obesogenic environment.

Ageing Res. Espada, L. Loss of metabolic plasticity underlies metformin toxicity in aged Caenorhabditis elegans. Fang, E. Cell , — Feng, X.

Berberine in cardiovascular and metabolic diseases: from mechanisms to therapeutics. Theranostics 9, — Gao, Z. Sirtuin 1 SIRT1 protein degradation in response to persistent c-Jun N-terminal kinase 1 JNK1 activation contributes to hepatic steatosis in obesity. Gao, Y. Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy.

Redox Biol. Ge, X. Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR and modulating SIRT1 expression. Aging 11, — Gerhart-Hines, Z. Cell 44, — Gomes, A. Gong, C. ILinduced acetylation of E2F1 aggravates oxidative damage of retinal pigment epithelial cell line.

Eye Res. Guo, Q. Tumor necrosis factor-α TNF-α enhances miRmediated endothelial senescence by targeting sirtuin1 SIRT1. Gurd, B. High-intensity interval training increases SIRT1 activity in human skeletal muscle.

Han, L. SIRT1 is regulated by a PPARγ-SIRT1 negative feedback loop associated with senescence. Nucleic Acids Res. Hayashida, S. Herzig, S. AMPK: guardian of metabolism and mitochondrial homeostasis. Hikosaka, K. Implications of NAD metabolism in pathophysiology and therapeutics for neurodegenerative diseases.

Hong, Y. The role of sirtuins in kidney diseases. Hu, M. SRC-3 is involved in maintaining hematopoietic stem cell quiescence by regulation of mitochondrial metabolism in mice. Blood , — Hu, C. Huang, Q. A SIRT1 activator, ginsenoside Rc, promotes energy metabolism in cardiomyocytes and neurons.

Huber, J. SIRT1-independent mechanisms of the putative sirtuin enzyme activators SRT and SRT Future Med. Ji, M.

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Jiang, M. Jiao, F. The beneficial roles of SIRT1 in neuroinflammation-related diseases. Joshi, A. Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration.

Juszczak, F. Critical role for AMPK in metabolic disease-induced chronic kidney disease. Karstoft, K. Resting metabolic rate does not change in response to different types of training in subjects with type 2 diabetes.

Kerr, J. Trends Neurosci. Knuiman, P. Select skeletal muscle mRNAs related to exercise adaptation are minimally affected by different pre-exercise meals that differ in macronutrient profile. Kosgei, V.

Sirt1-PPARS cross-talk in complex metabolic diseases and inherited disorders of the one carbon metabolism. Cells Koves, T. Peroxisome proliferator-activated receptor-γ co-activator 1α-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency.

Lamb, D. Aging 12, — Lamichane, S. MHY attenuates replicative cellular senescence in human endothelial progenitor cells SIRT1 signaling. Lan, Y. SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging.

Nucleic Acids 23, — Lan, F. Resveratrol-induced AMP-activated protein kinase activation is cell-type dependent: lessons from basic research for clinical application. Nutrients The purity of the cytosolic and nuclear fractions was confirmed by the absence of α-tubulin in the nuclear fraction and PARP in the cytosolic fraction.

d PIKE-A phosphorylation regulates its subcellular distribution. LN cells were transfected with GFP-PIKE-A WT or mutants SA, SD, SA, SD, SA, and SD , followed by subcellular fractionation. e PIKE-A phosphorylation regulates its subcellular distribution. LN cells were transfected with GFP-PIKE-A WT or mutants SA, SD, SA, SD, SA, and SD and then fixed and subjected to confocal imaging for the localization of PIKE-A and DAPI labeling for nuclei identification.

Therefore, we explored the role of AMPK on PIKE-A subcellular distribution. Notably, knocking down AMPK abolished nuclear PIKE-A Fig. We then examined the PIKE-A subcellular localization in LN cells in the presence or absence of numerous small molecules which can activate AMPK.

PIKE-A was usually localized in the cytoplasm, but translocated into the nucleus when treated with AICAR, Metformin, A, or H 2 O 2 , and at the same time increased phosphorylation of Thr in AMPKα Figure S2C.

We found that substitution of S or S alone or together with D resulted in increased PIKE-A nuclear translocation Fig. These data indicate that PIKE-A nuclear translocation correlated well with increased PIKE-A phosphorylation in an AMPK-dependent manner.

To explore whether PIKE-A interacts with β proteins, we conducted a co-immunoprecipitation assay and found that PIKE-A physically associated with β and serum starvation or hypoxia stimulation enhanced this interaction Fig.

Similarly, in the presence of AICAR, Metformin, A, or H 2 O 2 to stimulate PIKE-A phosphorylation, the binding between PIKE-A and β was increased Figure S3A. These data suggest that the association between PIKE-A and β was mediated by AMPK phosphorylation.

a Serum starvation enhances the interaction of PIKE-A and β. b Hypoxia enhances the interaction of PIKE-A and β. c The myc-PIKE-A WT or mutants SA, SD, SA, SD, SA, and SD were co-transfected with GFPβ into HEK cells.

GFPβ was immunoprecipitated and the co-precipitated proteins were analyzed using an anti-myc antibody. d β regulates AMPK-phosphorylated PIKE-A nuclear translocation.

To further confirm that the serine phosphorylation status on PIKE-A tightly correlated with the interaction between PIKE-A and β, we next performed a binding assay using PIKE-A mutants and β.

Noticeably, the depletion of β abolished PIKE-A nuclear translocation which escalated by AICAR, indicating that β is indispensable for AMPK-dependent PIKE-A nuclear translocation Fig. Together, our data suggest that β interacts AMPK-phosphorylated PIKE-A and stimulates its nuclear translocation.

Accordingly, we investigated the pathological consequence of PIKE-A nuclear translocation under energy stress, and observed that PIKE-A associated tightly with CDK4 in LN cells under serum starvation in the whole cell, particularly in nucleus, but not in cytoplasm Fig.

Similarly, in the presence of AICAR, Metformin, A, or H 2 O 2 stimulation the interaction was enhanced in the nucleus or whole cell, but not in cytoplasm Figure S4A and S4B. We next measured the interaction between PIKE-A WT or SA mutants and CDK4 when co-transfected with constitutively active TD or inactive TA mutant of AMPKα.

The GST-pull down assay displayed that compared with the prominent interaction between PIKE-A WT and CDK4, phospho-deficient PIKE-A mutant SA revealed lower binding affinity to CDK4.

As expected, PIKE-A SA barely interacted with CDK4 in the presence of AMPKα TA Fig. Furthermore, when co-transfected CDK4 with PIKE-A WT, SA or SD, the co-immunoprecipitation assay results showed that phospho-mimetic SD mutant of PIKE-A escalated the interaction between CDK4 and PIKE-A, whereas the SA mutant blocked this interaction Fig.

Hence, these data strongly suggest that AMPK phosphorylation regulates the interaction between PIKE-A and CDK4. a Serum starvation enhances the interaction of PIKE-A and CDK4. b Serum starvation enhances the interaction of PIKE-A and CDK4 in nucleus. c HEK cells were co-transfected with Flag-CDK4 with GST-PIKE WT or phospho-deficient GST-PIKE SA mutant in the presence of myc-AMPKα TD or myc-AMPKα TA.

The expression levels of transfected constructs were analyzed by immunoblotting. d Different GFP-tagged PIKE-A WT and mutants were transfected into HEK cells. Cell lysates were immunoprecipitated with anti-GFP or anti-CDK4 antibody, and co-precipitated proteins were analyzed by immunoblotting with anti-CDK4 or anti-GFP antibody.

To explore the effects of PIKE-A, CDK4, and their combined effect on downstream signaling cascades, we performed Rb phosphorylation analysis under different AMPK activation conditions. Rb is one of the major downstream targets of CDK4, and p-Rb signals are prominently elevated when CDK4 is overexpressed Our results showed that induction of AMPK activity by serum starvation and the well-characterized stimuli blocked the Rb phosphorylation level Fig.

In contrast, when we knocked down AMPK, Rb phosphorylation was elevated Fig. Then we investigated the effect of AMPK on phosphorylation of PIKE-A in mediating CDK4-Rb signaling cascades. Overexpression of PIKE-A WT or SA but not SD strongly elevated Rb phosphorylation, in alignment with what was observed in GFP empty vector-transfected cells, and these effects were abolished when knocked down by CDK4 Fig.

a Serum starvation decreases Rb phosphorylation. Cell lysates were immunoblotted using anti-p-Rb antibody. b AMPK activators inhibit Rb phosphorylation. LN cells were treated with AICAR, Metformin, A, and H 2 O 2. Then Rb, as a downstream effector of CDK4, was analyzed by immunoblotting.

c Knock down of AMPKα increases Rb phosphorylation. Rb phosphorylation was analyzed by immunoblotting in AMPKα shRNA or control vector-transfected LN cells.

d PIKE-A phosphorylation suppresses CDK4-mediated Rb phosphorylation. In LN cells, CDK4 shRNA or control shRNA were transfected with GFP-PIKE-A WT and mutants SA and SD. e PIKE-A phosphorylation inhibits CDK4 activity in vitro. Rb phosphorylation statuses were analyzed by immunoblotting.

To examine whether PIKE-A directly inhibits CDK4 activity, we performed in vitro CDK4 kinase assay employing the Rb peptide as a CDK4 substrate. Collectively, our data support that PIKE-A phosphorylation suppresses the CDK4-Rb pathway, which is mediated by cellular energy stress-induced AMPK activation.

We performed cell proliferation, cell viability, and cell cycle assay in LN GBM cells transfected with GFP vector, GFP-PIKE-A WT, SA, and SD mutant, respectively. As expected, PIKE-A WT strongly conferred cell proliferation potential. However, PIKE-A SD mutant, which mimics PIKE-A phosphorylation by AMPK, lost the ability to promote cell proliferation and cell viability Fig.

Next, we monitored the effect of PIKE-A WT or SA mutant on cell proliferation, cell viability, and cell cycle when co-transfected with active AMPK.

The results show that active AMPK strongly inhibits PIKE-A WT but not PIKE-A SA mutant cell proliferation, cell viability, and cell cycle Fig. Therefore, our findings indicate that AMPK-phosphorylated PIKE-A induces cell cycle arrest and inhibits cell proliferation.

a LN cells were transfected with GFP-PIKE-A WT and mutant SA and SD and cell proliferation was tested by cell counting.

b LN cells were transfected with GFP-PIKE-A WT and mutant SA and SD and cell cycle distributions were analyzed by flow cytometry. Lower: Cell proliferation index PI was calculated based on the indicated equation and is shown. c LN cells were co-transfected with GFP-PIKE-A WT or SA mutant and constitutively active mutant of AMPKα and cell proliferation was determined by cell counting.

d LN cells were co-transfected with GFP-PIKE-A WT or SA mutant and constitutive active mutant of AMPKα. Cell cycle distributions were analyzed by flow cytometry. Extensive studies have revealed that the PIKE-A has an essential function in promoting cancer cell survival and growth and preventing cell apoptosis 1 , 2 , 3 , 4.

Recent studies have revealed that PIKE-A can be phosphorylated by CDK5, Akt, and Fyn on Ser ref. In addition, it has been shown that PIKE-A can also be regulated by extracellular signals, such as epidermal growth factor EGF. Therefore, PIKE-A can integrate and coordinate both extracellular and intracellular signals under energy stress.

AMPK detects cellular energy stress, which modulates cellular metabolism balance and limits cell growth AMPK accomplishes its regulatory functions either via direct and rapid phosphorylation of the metabolic enzymes or eliciting indirectly target gene expression 15 , Our present study identifies that AMPK directly phosphorylates PIKE-A in response to cellular energy stress.

It is worth noting that the phosphorylation sites of PIKE-A are Ser and Ser, which are in the PH domain Fig. Notably, our subsequent data indicated that these two phosphorylated sites of PIKE-A display the same biological function. Our previous report showed that the GTPase domain of PIKE-A is responsible for binding AMPK We propose that this binding is conducive and sufficient for PIKE-A phosphorylation by AMPK.

Further evidence supports that a physiological function of PIKE-A phosphorylation in cellular energy response is PIKE-A nuclear translocation, which is dependent on AMPK activation Fig. The mechanisms underlying the nuclear translocation of PIKE-A and its role in tumorigenesis were not previously well understood.

We demonstrate here that the nuclear trafficking of PIKE-A is regulated by , which contains a bipartite nuclear localization signal NLS and consequently promotes PIKE-A binding to CDK4 tightly in the nucleus Figs. This interaction shields CDK4 and disrupts the CDK4—CyclinD1 complex formation and Rb activity, and further induces cell cycle arrest Figs 5 and 6.

Therefore, PIKE-A phosphorylation is likely to play a role in maintaining cellular energy homeostasis. Energy-stress-induced PIKE-A phosphorylation and nuclear translocation mediated by AMPK activation reduces energy expenditure and cell growth, possibly by inhibiting the CDK4—Rb pathway.

Our study uncovers a mechanism of cellular energy and crosstalk with PIKE-A through mechanisms of AMPK regulation.

Considering the general role of PIKE-A in promoting cell proliferation and inhibiting apoptosis through PIKE-A modification such as phosphorylation and cleavage, etc.

When cell conditions are normal or favorable, PIKE-A activates Akt and promotes cell proliferation. However, cell proliferation should not proceed if cellular energy is limited, and such conditions would allow AMPK activation to maintain basic survival. Therefore, the direct phosphorylation of PIKE-A in an AMPK-dependent manner provides a mechanism to ensure that cell proliferation occurs only when favorable growth conditions are available.

The phosphorylation of PIKE-A by AMPK adds new dimensions to both energy stress-mediated regulations of PIKE-A and the pathomechanisms of AMPK in controlling of cell growth. Indeed, phosphorylation of PIKE-A has the significant benefit of cell proliferation blockade and provides new target for therapeutic intervention of cancer.

Thus, high activation of AMPK may pave the way for improved outcomes for cancer patients with high PIKE-A expression. This cell line was a gift from Dr. Louis, MO, USA. Antibody against myc, GST, p-AMPK α T , AMPK α, p-AMPK α substrate, PARP, α-Tubulin, p-Rb, Rb was from Cell Signaling Technology Beverly, MA, USA.

Antibody against Flag, CDK4, and PIKE-A were purchased from Santa Cruz Biotechnology Santa Cruz, CA, USA. Control and targeted hairpins against AMPK α shAMPKα and β shβ were purchased from Thermo Fisher Scientific Waltham, MA, USA.

Selected reactions were carried out in the presence or absence of active AMPKα1β1γ1. The gels were dried with a Model Gel Dryer Bio-Rad and phosphorylated proteins were visualized by autoradiography.

LN cells were collected and wash once with ice-cold 1× phosphate-buffered saline PBS. The cell pellet was resuspended in CER I buffer. These methods were performed essentially as described previously Cell viability was determined by using CellTiter 96® AQueous One Solution Cell Proliferation Assay MTS Promega.

The stained cells were passed through a nylon-mesh sieve to remove cell clumps and were analyzed by a FACScan flow cytometer. Samples were resolved by SDS-PAGE, and phosphorylation of Rb was measured by WB analysis.

Data were analyzed by log-rank test and KM plots were drawn by Graphpad Prism 7. Light therapy has been studied through intensive scientific research over the past 40 years, specifically under an area known as low level laser therapy, or nowadays referred to as photobiomodulation.

It is understood that the targeted wavelength of the red light spectrum, to nm, can penetrate the skin millimeters, working from the inside-out to enhance mitochondrial function and thus benefit the skin.

It has been noted in research that nm wavelength is closest to the resonant frequency of cell tissue and can subsequently be absorbed better in the hemoglobin, the carrier of oxygen in red blood cells.

Near-infrared NIR wavelengths that function at the or nm level have been shown to penetrate far deeper beneath the skin to tissue and bone. Based on research at NASA, NIR emitted through color specific LED bulbs operate by activating color sensitive chemicals in body tissues.

The combination of red light, which offers healing to the skin, and NIR, as healing to deeper organs, means a light therapy that improves our energy and healing, upgrades our health, enhances how the brain works because its energy workload is freed up and it can achieve higher grade energy production.

Research study programs reveal health benefits that include enhanced blood circulation, anti-inflammatory effects, increased muscle recovery, improved skin tone and glow, reduced wrinkles and scars, improved wound healing, pain reduction, lymphatic flow boost, increased cellular growth, and even enhanced fertility and increased testosterone.

A reduction of inflammation on both the skin and inner organs improves health and aids the reduction of inflammation in the brain to improve brain function.

Take any opportunity you have to spend time outside in good, natural light. This is especially beneficial at the start of the day. One of the best ways to handle jet lag is to get up at dawn on your first wake up day in your new time zone and be outside, under the light looking towards the sun, whether cloudy or clear skies.

Also take any opportunity to walk to work, school or the stores, and sit outside for lunch. The environment of Samahita is a natural light and fresh air paradise. This is one of the reasons you can leave feeling better as it enhances all the other life-giving health practices you do here.

We also go a few steps further to enhance your brain wellness in our Brain Health Upgrade program. One of the therapies in this program involves mitochondria enhancing red and NIR light therapy.

Improved cellular functioning and energy production helps your brain, similar to providing a cleaner more efficient energy supply to your car or house. The focus of this program is to improve the production of that energy supply, enhance its delivery, and optimize its use, for and within the brain.

The challenges of the modern world cannot allow us to take for granted that our brain is just going to perform well. The statistics show the shocking rise of dementia and related mental pathologies with the unfortunate reality of modern life being further removed from nature and her glorious inputs.

Yoga, meditation and upgraded actions are not just needed, they are unavoidably essential today. As a result, Paul occupies a unique space to impart genuine teaching and science on the breath, body, and meditative practices, seen as a Teacher-of-teachers and identified to carry on the tradition of Pranayama.

His sincere and ongoing role is to teach, write and research, to help put out experienced and authentic information on these areas of how we live, breathe and be, to help people improve their mental and physical health, and live more fulfilling lives.

For more on his background see his bio. This site uses cookies. By continuing to browse the site, you are agreeing to our use of cookies.

Logically, a drop in performance reduced gain can be one outcome. Alternatively, as the pigs try to eat their energy requirement they might increase feed intake to consume the same amount of energy to reach their genetic growth potential.

The second coping strategy was observed in this trial. All pigs showed similar weight gains and reached similar slaughter weights within the same time. However, the animals in the NC group had to significantly increase their feed intake to reach the same energy intake and maintain growth at the same level as the other 2 groups.

That is a clear indication that dietary energy was reduced to a level that forced the pigs to adapt in the NC group. On the other hand, the animals in both the PC group and the GAA group maintained similar levels of feed intake. The pigs of those groups therefore received comparable energy levels.

The addition of GAA must have improved the cellular creatine pool, resulting in enhanced intra-cellular energy efficiency.

That energy contribution reduced the need for currently expensive dietary energy: 0. This is likely the first trial proving that the well-established poultry application, using GAA to spare dietary energy, could be transferred to fattening pigs.

Supplying cellular physiological energy by improving creatine supply to the animals allowed a reduction in dietary energy. Therefore, 0. Future studies should confirm that finding as well as examine the full energy sparing potential of GAA in grower-finisher pigs.

As components with high energy contents such as oil are very high cost, reducing their inclusion by adding GAA delivers consistent economic benefits when ­producing grower-finisher pigs.

AlzChem Group AG , is a vertically integrated manufacturer of various chemical products based on the NCN chain. AlzChem has a worldwide leading position in selected markets, including nutritional feed additives, food supplements and agriculture.

Alzchem has been the leading supplier for creatine for more than 25 years. Alzchem produces Creamino and Creapure exclusively in Germany. More about AlzChem. Fattening pigs in one of the experimental pens.

Photo: Joaquín Morales Enhancing cellular energy in grower-finisher pigs. AlzChem Group AG Partner profile. Photo: Joaquín Morales. Supplementing creatine It has been shown that supplementing creatine or its meta­bolic precursor guanidino-acetic acid GAA to diets of humans or animals can replenish creatine and alter the available creatine pool in the cells, improving physical and zootechnical performance.

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How customer reviews and ratings work Customer Reviews, including Product Star Ratings help customers to learn more about the product and decide whether it is the right product for them. Learn more how customers reviews work on Amazon. Contrary to the anti-aging effect observed in young nematodes, metformin can aggravate aging-related mitochondrial dysfunction and lead to a shortening of life span in old Caenorhabditis elegans Espada et al.

Metformin plays a beneficial role by activating SIRT1-mediated, AMPK-independent autophagy pathways, and also combats the inhibition of intracytoplasmic P53 on parkin-mediated mitophagy, thus maintain mitochondrial quality Song et al. This result is similar to another study, metformin promotes the expression of mitophagy-related genes to restore parkin-mediated mitophagy pathway activity, maintain mitochondrial integrity and cell survival, protect cells from high glucose-induced damage Zhao and Sun, However, the association between mitophagy and SIRT1 has not been fully elucidated.

Moreover, the tricyclopyranone compound CP2 Zhang et al. The imbalance of energy supply and demand make the body in a state of energy stress. Cells often redistribute the energy generated to important mechanisms and activities when the energy supply cannot meet the energy demand.

As the main energy producer, the energy production of mitochondria is closely regulated by a variety of energy receptors in cells. Promoting the biosynthesis and function of mitochondria to produce enough ATP to meet the energy gap of cells has become an important means to break the energy stress state of cells.

However, the expression and activity of SIRT1 decreased significantly in pathological conditions such as aging or age-related diseases. In this review, we discussed that precise regulation of SIRT1 activity at all levels can eliminate cellular energy stress.

We also discussed that SIRT1 molecular activator can promote the activity and expression of SIRT1 and play a useful role, which can be used as promising methods for the treatment of aging, neurodegenerative diseases, metabolic diseases, and other diseases.

Other studies also have found that a long-term CR diet can improve metabolism and promote fat loss, but the effect of fat loss will be quickly reversed once stopped Melo et al. Therefore, I think we can implement CR with a continuous and progressive degree on mice to observe the effect on the body compared with the effect of CR with a constant degree of persistence.

At the same time, the effect on weight reversal was observed by progressively reducing the extent of the CR diet rather than abruptly stopping the CR diet at the end. On the other hand, our study found that mitochondrial function is impaired under pathological conditions, which may be partly due to changes in mitochondrial dynamics and increased mitochondrial fragmentation Yang D.

The SIRT1 pathway is beneficial to restore the quality and efficiency of mitochondria, so promoting the dynamic recovery of mitochondria is expected to be achieved by promoting the biosynthesis of mitochondria. Previous studies mainly focused on the nuclear-cytoplasmic shuttle of SIRT1. The subcellular localization of SIRT1 shows that SIRT1 in mitochondria can also communicate with SIRT1 in the cytoplasm, which provides a basis for us to accurately regulate the function of mitochondria through SIRT1.

In conclusion, although the mechanisms of SIRT1 and SIRT1-related activators in anti-aging and age-related diseases have not been clarified in detail, there is a complex and inseparable relationship between the fine regulation mechanism of SIRT1 activity and expression and the mitochondria function.

Therefore, it is extremely important to further clarify the causal relationship between them to provide direction for the promotion of human health and anti-aging. YF, JY and FH: conception, designing, and writing of the manuscript.

XW, JY, DY, WY, XL and QZ: assisted in literature search, conception, and writing of the manuscript. FH, YL and GW: conception and revising the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by grants from the National Natural Science Foundation of China and , Natural Science Foundation of Jiangxi Province BCB and BABL , and Youth Team Project of the Second Affiliated Hospital of Nanchang University YNTD The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

We apologize in advance to those researchers who contributed to the field and their publications were not listed in this review. Bai, L. Attenuation of Pb-induced Aβ generation and autophagic dysfunction via activation of SIRT1: neuroprotective properties of resveratrol.

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Screening SIRT1 activators from medicinal plants as bioactive compounds against oxidative damage in mitochondrial function.