Challenge

What are some of the most promising natural compounds we can use to slow aging?

Image credit: https://pubchem.ncbi.nlm.nih.gov/compound/Ginseng#section=2D-Structure

Brett M. Dec 03, 2020

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It is one thing to come up with a drug in an attempt to extend the lifespan, or use a drug off-label to take advantage of its anti-aging effects. However, can we simply rely on naturally occurring substances that are found in the environment? What are some naturally occurring compounds that show promise in promoting longevity? Alternatively, it may necessary to combine natural and synthetic compounds to reap the most benefit out of their anti-aging properties.

For example, panax ginseng, and more specifically, the ginsenoside (active component of ginseng) compounds are known for their use to promote longevity and provide rejuvenating effects in the body    .  Ginseng gintonin, which is most commonly provided as a herbal medicine, has been found to protect the brain from age-related neurodegenerative diseases, such as Alzheimer's, and even the process of aging itself     . It is a glycolipoprotein and its active ingredient is lysophosphatidic acids (LPA) which has been found to be largely composed of linoleic acid     --which is interesting, since LPAs in animals are typically composed of oleic acid, palmitic acid, or stearyl acid     . This makes LPAs found in gintonin unique. 

Some of the specific anti-aging-related properties of gintonin include the enhancement of cognitive functions that are primarily hippocampal-dependent    , the reversal of age-related reductions in long-term potentiation and cognitive performance     , and the stimulation of cell proliferation and differentiation--processes normally impeded by the aging process     . Importantly, preclinical models of experimentally-induced aging suggest that LPA1 receptors may play a key role in the cognitive decline associated with aging and neuronal senescence. In fact, gintonin-induced restoration of cognitive function in preclinical aging models was found to associate with increased expression of LPA1 receptor expression in the hippocampus    , and LPA1 receptor knockout mice were found to exhibit deficits in cognitive function and attention     . 

This provides some promising evidence for ginseng gintonin in the fight against the aging process. But, I'm curious--what are some other naturally-derived compounds that can be used to combat aging and promote longevity?

[1]Gawa-Ochiai K, Kawasaki K. Panax ginseng for frailty-related disorders: a review. Front Nutr 2018;5:140

[2]Kim HJ, Jung SW, Kim SY, Cho IH, Kim HC, Rhim H, et al. Panax ginseng as an adjuvant treatment for Alzheimer’s disease. J Ginseng Res 2018;42:401–11.

[3]Hwang SH, Shin TJ, Choi SH, Cho HJ, Lee BH, Pyo MK, et al. Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity. Mol Cells 2012;33:151–62.

[4]Tigyi G, Miledi R. Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytes and neurite retraction in PC12 pheochromocytoma cells. J Biol Chem 1992;267:21360–7.

[5]Kim S, Kim MS, Park K, Kim HJ, Jung SW, Nah SY, et al. Hippocampusdependent cognitive enhancement induced by systemic gintonin administration. J Ginseng Res 2016;40:55–61.

[6]Nam SM, Hwang H, Seo M, Chang BJ,Kim HJ, Choi SH, et al. Gintonin attenuates d-galactose-induced hippocampal senescence by improving long-term hippocampal potentiation, neurogenesis, and cognitive functions. Gerontology 2018;64:562–75.

[7]Kim HJ, Jung SW, Kim SY, Cho IH, Kim HC, Rhim H, et al. Panax ginseng as an adjuvant treatment for Alzheimer’s disease. J Ginseng Res 2018;42:401–11.

ginseng gintonin lpa ginseng natural longevity

Creative contributions

Curcumin Derived From Turmeric

Ruby Grewal Dec 03, 2020

I was thinking along the same lines, and another naturally-derived compound that can promote longevity is curcumin. Curcumin is a polyphenol that is the primary therapeutic component of the spice turmeric. Turmeric has been used for thousands of years in cooking and the U.S. FDA has approved curcumin as “Generally Recognized as Safe”. Doses as high as 12 g per day have been shown to be well tolerated in humans.    

Studies in mice, nematodes, and fruit flies have shown that curcumin supplementation extends life span, ameliorates cognitive decline, and decreases both systemic inflammation and neuroinflammation. These effects appear to be related to curcumin’s anti-oxidant properties.                         

Curcumin has many different targets and mechanisms of action, including anti-bacterial, anti-oxidant, wound-healing and antitumor properties. It modulates multiple cell signalling molecules, including pro-inflammatory cytokines (tumor necrosis factor alpha), interleukin 1ß and 6, NF-K ß, COX-2, STAT3.     

The benefit of using a highly pleiotropic molecule such as curcumin is that in a process such as aging, which has at least 9 main interconnected components,      a molecule that targets more than one process is more likely to prove beneficial.

Curcumin also has evidence of benefit in human trials. In clinical trials, curcumin was shown to reduce symptoms of age-related diseases such as rheumatoid arthritis,      pancreatic cancer,      and colorectal cancer.     

While most of the curcumin clinical studies have focused on its effect on various disease states, a study demonstrated that it was also beneficial in healthy middle-aged people, and was shown to improve working memory.     

One of the hurdles that needs to be overcome in using curcumin therapeutically is its low bioavailability. However, studies have shown a number of ways to increase its bioavailability, including co-administration with piperine, found in black pepper, which increased systemic bioavailability by as much as 154%.      Another consideration is that although curcumin use doesn’t appear to have any significant adverse effects in the short-term, long-term studies have not been done.

So overall, in animal models curcumin has been shown to increase life span, and while this hasn’t yet been shown in human studies, clinical trials have shown the beneficial effect of curcumin on a number of age-related diseases.

[1]Fadus MC, Lau C, Bikhchandani J, Lynch HT. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent. J Tradit Complement Med. 2016 Sep 9;7(3):339-346. PMID:28725630. PMCID: PMC5506636 doi: 10.1016/j.jtcme.2016.08.002

[2]Liao V.H.C., Yu C.W., Chu Y.J., Li W.H., Hsieh Y.C., Wang T.T. Curcumin-mediated lifespan extension in Caenorhabditis elegans. Mech. Ageing Dev. 2011;132:480–487. PMID: 21855561. doi: 10.1016/j.mad.2011.07.008.

[3]Lee K.-S., Lee B.-S., Semnani S., Avanesian A., Um C.-Y., Jeon H.-J., Seong K.-M., Yu K., Min K.-J., Jafari M. Curcumin Extends Life Span, Improves Health Span, and Modulates the Expression of Age-Associated Aging Genes in Drosophila melanogaster. Rejuvenation Res. 2010;13:561–570. PMID: 20645870. doi: 10.1089/rej.2010.1031.

[4]Soh J.W., Marowsky N., Nichols T.J., Rahman A.M., Miah T., Sarao P., Khasawneh R., Unnikrishnan A., Heydari A.R., Silver R.B., et al. Curcumin is an early-acting stage-specific inducer of extended functional longevity in Drosophila. Exp. Gerontol. 2013;48:229–239. PMID: 23063786. doi: 10.1016/j.exger.2012.09.007.

[5]Shen L.R., Parnell L.D., Ordovas J.M., Lai C.Q. Curcumin and aging. BioFactors. 2013;39:133–140. PMID: 23325575. doi: 10.1002/biof.1086.

[6]Sikora E., Scapagnini G., Barbagallo M. Curcumin, inflammation, ageing and age-related diseases. Immun. Ageing. 2010;7:1. PMID: 20205886. PMCID: PMC2827376. doi: 10.1186/1742-4933-7-1.

[7]Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013;15(1):195-218. PMID: 23143785. PMCID: PMC3535097. doi:10.1208/s12248-012-9432-8.

[8]López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. PMID: 23746838; PMCID: PMC3836174. doi:10.1016/j.cell.2013.05.039.

[9]Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016;19(8):717-729. PMID: 27533649. PMCID: PMC5003001. doi:10.1089/jmf.2016.3705

[10]Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, Ng CS, Badmaev V, Kurzrock R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008 Jul 15;14(14):4491-9. PMID: 18628464. doi:10.1158/1078-0432.CCR-08-0024.

[11]Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia [published correction appears in Cancer Prev Res (Phila). 2012 Dec;5(12):1407. Dosage error in article text]. Cancer Prev Res (Phila). 2011;4(3):354-364. PMID: 21372035. PMCID: PMC4136551. doi:10.1158/1940-6207.CAPR-10-0098.

[12]DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79. PMID: 23013352; PMCID: PMC3518252. doi: 10.1186/1475-2891-11-79.

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Flavonoids in Blueberries

Shubhankar Kulkarni Dec 03, 2020

Blueberries are rich in flavonoids and these flavonoids possess antioxidant and anti-inflammatory properties. A 12-week study investigating the effects of blueberry concentrate supplementation showed an improvement in brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants aged 67.5 ± 3 years consumed 30 ml blueberry concentrate, which gives 387 mg anthocyanidins. Participants undertook cognitive function tests and simultaneous functional magnetic resonance images were continuously acquired. Participants who took the blueberry concentrate also showed improvement in working memory compared to the placebo group.     
Another study examined the effects of daily blueberry consumption (22 g freeze-dried blueberry powder) for 8 weeks on blood pressure and arterial stiffness in postmenopausal women. After 8 weeks, systolic blood pressure, diastolic blood pressure, and brachial-ankle pulse wave velocity were significantly lower than baseline levels in the group that consumed the blueberry powder. Nitric oxide levels were greater in the blueberry powder group compared to baseline levels.     

[1]Joanna L. Bowtell, Zainie Aboo-Bakkar, Myra E. Conway, Anna-Lynne R. Adlam, and Jonathan Fulford. Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation. Applied Physiology, Nutrition, and Metabolism. 42(7): 773-779. https://doi.org/10.1139/apnm-2016-0550

[2]Sarah A. Johnson, Arturo Figueroa, Negin Navaei Alexei Wong, Roy Kalfon, Lauren T. Ormsbee, Rafaela G. Feresin, Marcus L. Elam, Shirin Hooshmand, Mark E. Payton, Bahram H. Arjmandi. Daily Blueberry Consumption Improves Blood Pressure and Arterial Stiffness in Postmenopausal Women with Pre- and Stage 1-Hypertension: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Published:January 07, 2015 DOI:https://doi.org/10.1016/j.jand.2014.11.001

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Shubhankar Kulkarni4 years ago

Fisetin (3,3′,4′,7-tetrahydroxyflavone, a flavonoid) from strawberry, apple, persimmon, grape, onion, and cucumber.

A study screened flavonoids for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. Of the flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. In older wild-type mice, administration of fisetin restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.

Reference: Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28. doi:10.1016/j.ebiom.2018.09.015

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Biophenols from olives and nuts reduce cognitive decline and improve cardiovascular markers

Shubhankar Kulkarni Dec 03, 2020

Olive is one of the main components of the MedDi (Mediterranean diet) and MIND (Mediterranean-DASH (Dietary Approaches to Stop Hypertension) Intervention for Neurodegenerative Delay) diets and its potential health benefits are suggested due to the presence of its bioactive constituents such as oleic acids and phenolic compounds (biophenols). The study suggests that MedDi and MIND diets help in maintaining the cognitive function in Alzheimer's disease.     
Nuts are known for their cholesterol-lowering effects. After a 4-week background diet enriched with virgin olive oil, walnuts, or almonds, total cholesterol and LDL/HDL ratios decreased. LDL-cholesterol, which is one of the cardiovascular risk markers, decreased more than what was predicted based on the diet (consumption).     

[1]Omar, S.H. Mediterranean and MIND Diets Containing Olive Biophenols Reduces the Prevalence of Alzheimer’s Disease. Int. J. Mol. Sci. 2019, 20, 2797.

[2]N.R.T. Damasceno, A. Pérez-Heras, M. Serra, M. Cofán, A. Sala-Vila, J. Salas-Salvadó, E. Ros. Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers. Published:March 23, 2011DOI:https://doi.org/10.1016/j.numecd.2010.12.006

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Natural compounds found in ginger extracts

Jamila Dec 03, 2020

Previous studies have supported that ginger has anti-inflammatory effects and antioxidant properties. The main compounds in ginger with specialized properties are gingerols, paradols, and shogaols.     

In terms of aging and age-related studies, there has been some research. Researchers suggest that ginger's natural compounds can protect against age-associated diseases like Alzheimer's, diabetes, Parkinson's disease, and much more.             Specifically, the usage of 6-gingerol prevented amyloid-beta plaque cytotoxicity in neuronal cells, thus showing that 6-gingerol exerts a neuroprotective effect in vitro.      In another study, researchers gave 800mg/kg ginger extract to diabetic mice. The fasting blood glucose levels were significantly lower in the group using the ginger extract.     

Zhou and colleagues found that ginger extracts were able to increase the lifespan of Drosophila melanogaster. In the study, fruit flies receiving 0.5mg/mL ginger didn't have an improved lifespan. However, 1mg/mL or 2mg/mL ginger extract increased the fruit flies' mean lifespan.     Although the research is promising, further work needs to be done using ginger and its natural compounds.

[1]Nile, Shivraj Hariram, and Se Won Park. "Chromatographic analysis, antioxidant, anti-inflammatory, and xanthine oxidase inhibitory activities of ginger extracts and its reference compounds." Industrial Crops and Products 70 (2015): 238-244.

[2]Shanmugam, Kondeti Ramudu, et al. "Protective effect of dietary ginger on antioxidant enzymes and oxidative damage in experimental diabetic rat tissues." Food Chemistry 124.4 (2011): 1436-1442.

[3]Park, Gunhyuk, et al. "6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation." Acta Pharmacologica Sinica 34.9 (2013): 1131-1139.

[4]Zeng, Gao-feng, et al. "Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats." Rejuvenation Research 16.2 (2013): 124-133.

[5]Lee, Chan, et al. "[6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system." Food and chemical toxicology 49.6 (2011): 1261-1269.

[6]J. A. O. Ojewole, "Analgesic, anti-inflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats," Phytotherapy Research, vol. 20, no. 9, pp. 764–772, 2006.

[7]Zhou, Yu-zhi, et al. "Ginger extract extends the lifespan of Drosophila melanogaster through antioxidation and ameliorating metabolic dysfunction." Journal of Functional Foods 49 (2018): 295-305.

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Astaxanthin as a neuroprotector

Brett M. Dec 17, 2020

A variety of processes contribute to cell aging, such as oxidative stress, inflammation, and apoptosis     . Reactive oxygen species highly contribute to the detrimental outcomes of oxidative stress that can arise from mitochondrial dysfunction      which can eventually lead to pathology involved in many neurodegenerative disorders    .  

Recently, the lipid-soluble keto-carotenoid known as astaxanthin has shown promise in providing neuroprotection in experimental models         . For the most part, astaxanthin, or AST (or ASX, depending where you are reading about this compound), is isolated from red algae, but there is evidence that this compound can be extracted from a variety of marine animals including shrimp, lobster, trout, and salmon     . One of the most challenging tasks in a compounds ability to provide neuroprotection is its ability to pass the blood-brain barrier, but due to AST's highly unsaturated lipid structure (among other biochemical properties), this compound is able to freely pass through this barrier and access the central nervous system     . 

AST was found to block macrophage migration inhibitory factor which ultimately inhibits the production and release of pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-alpha, as well as other inflammatory mediators including monocyte chemoattractant protein-1    .  As for its role in oxidative stress, AST was found to reduce the ratio between phosphorylated and unphosphorylated extracellular protein kinase (p-ERK/ERK)         , of which an increase has been implicated in the generation of reactive oxygen species and endoplasmic reticulum stress     .  Additionally, it has been shown that AST can protect against apoptosis through this suppressed ratio as well as through its ability to suppress other elements involved in apoptosis, including caspase 3 and 9, cytochrome c, and Bax/Bcl2 ratios        . 

When it comes to studying the possible health benefits in humans, there is conflicting evidence that this compound improves cognitive functioning         , which is known to decline with age. This controversy likely arises from the methodology used and the age-group by which AST was administered in the studies reported here     , while AST was administered to older adults diagnosed with mild cognitive impairments in this study     . Thus, further investigation needs to be conducted on the range (or lack) of benefits that AST can provide, specifically by focusing on the possible influence of baseline cognitive functioning (i.e., health status) prior to treatment and whether age plays a critical role in its neuroprotective properties.

Nevertheless, it is apparent that AST can provide neuroprotection in preclinical models. And that, this compound may have merit in preserving cognitive function as we age. Future studies will be needed to truly address whether AST can be categorized as a cognitive preserver or cognitive enhancer (or perhaps both?).

[1]Fakhri, S.; Abbaszadeh, F.; Dargahi, L.; Jorjani, M. Astaxanthin: A mechanistic review on its biological activities and health benefits. Pharmacol. Res. 2018, 136, 1–20

[2]Bhat, A.H.; Dar, K.B.; Anees, S.; Zargar, M.A.; Masood, A.; Sofi, M.A.; Ganie, S.A. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed. Pharmacother. Biomed. Pharmacother. 2015, 74, 101–110

[3]Fakhri, S.; Dargahi, L.; Abbaszadeh, F.; Jorjani, M. Effects of astaxanthin on sensory-motor function in a compression model of spinal cord injury: Involvement of ERK and AKT signalling pathway. Eur. J. Pain 2019, 23, 750–764

[4] Fakhri, S.; Dargahi, L.; Abbaszadeh, F.; Jorjani, M. Astaxanthin attenuates neuroinflammation contributed to the neuropathic pain and motor dysfunction following compression spinal cord injury. Brain Res. Bull. 2018, 143, 217–224

[5]Kidd, P. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern. Med. Rev. A J. Clin. Ther. 2011, 16, 355–364.

[6]Tan BJ, Chiu GN. Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis. Int J Oncol. 2013 May;42(5):1605-12. doi: 10.3892/ijo.2013.1843. Epub 2013 Mar 1. PMID: 23467622.

[7]Masoudi, A.; Dargahi, L.; Abbaszadeh, F.; Pourgholami, M.H.; Asgari, A.; Manoochehri, M.; Jorjani, M. Neuroprotective effects of astaxanthin in a rat model of spinal cord injury. Behav. Brain Res. 2017, 329, 104–110.

[8]Nouchi R, Suiko T, Kimura E, Takenaka H, Murakoshi M, Uchiyama A, Aono M, Kawashima R. Effects of Lutein and Astaxanthin Intake on the Improvement of Cognitive Functions among Healthy Adults: A Systematic Review of Randomized Controlled Trials. Nutrients. 2020 Feb 27;12(3):617. doi: 10.3390/nu12030617. PMID: 32120794; PMCID: PMC7146131.

[9]Ito N, Saito H, Seki S, Ueda F, Asada T. Effects of Composite Supplement Containing Astaxanthin and Sesamin on Cognitive Functions in People with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2018;62(4):1767-1775. doi: 10.3233/JAD-170969. Erratum in: J Alzheimers Dis. 2019;68(2):839. PMID: 29614679; PMCID: PMC5900571.

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Sargaquinoic acid from brown alga Sargassum sagamianum

Shubhankar Kulkarni Feb 02, 2021

The plastoquinone sargaquinoic acid is a major component of brown alga Sargassum sagamianum and is known to be involved in neurite growth and survival.      It is also known for its antioxidant and anti-inflammatory properties. A study showed that sargaquinoic acid inhibited tumor necrosis factor (TNF)-α and it protects against TNF-α-induced vascular inflammation via inhibition of the NF-κB pathway. These data suggest that sargaquinoic acid may be used as a therapeutic agent for vascular inflammatory diseases like atherosclerosis.     

[1]Hur S, Lee H, Kim Y, Lee BH, Shin J, Kim TY. Sargaquinoic acid and sargachromenol, extracts of Sargassum sagamianum, induce apoptosis in HaCaT cells and mice skin: Its potentiation of UVB-induced apoptosis. Eur J Pharmacol. 2008 Mar 17;582(1-3):1-11. doi: 10.1016/j.ejphar.2007.12.025. Epub 2007 Dec 28. PMID: 18243174.

[2]Gwon WG, Lee B, Joung EJ, Choi MW, Yoon N, Shin T, Oh CW, Kim HR. Sargaquinoic acid inhibits TNF-α-induced NF-κB signaling, thereby contributing to decreased monocyte adhesion to human umbilical vein endothelial cells (HUVECs). J Agric Food Chem. 2015;63:9053–61.

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Rapamycin from Streptomyces hygroscopicus strain AY B994

Shubhankar Kulkarni Feb 02, 2021

We have talked about the lifespan-extending properties of Rapamycin a lot in other sessions (1, 2, and 3). I will briefly mention it here since Rapamycin is also a natural compound. Rapamycin is used as an immunosuppressant and can be isolated from the bacteria Streptomyces hygroscopicus strain AY B994. Rapamycin is a potent inhibitor of the TOR pathway and it extended median and maximal lifespans of both male (by about 9%) and female (by about 14%) mice at a concentration of 14 mg/ kg.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Quercetin increases stress resistance and longevity

Shubhankar Kulkarni Feb 03, 2021

Quercetin is a flavonoid found in apples, cherries, citrus fruits, honey, onions, and green leafy vegetables.      A study showed that 330 mM quercetin increased oxidative stress resistance and longevity by about 60% in yeast and concentrations up to 200 mM increased resistance to thermal and oxidative stress and extended the lifespan of C. elegans by 18%. Quercetin modulates genes related to nutrient-sensing pathways like daf-2. Quercetin reversed the cognitive deficits in aged and ethanol-intoxicated mice. Quercetin glycosides like quercetin 3'-O-b-D-glucopyranoside and quercetin 3-O-b-D-glucopyranoside-(4/1)-b-Dglucopyranoside and methylated derivatives of quercetin - isorhamnetin and tamarixetin have also been shown to extend lifespan and promote its anti-aging effects.     

[1]G. Mohan Shankar, Jayesh Antony, Ruby John Anto, Chapter Two - Quercetin and Tryptanthrin: Two Broad Spectrum Anticancer Agents for Future Chemotherapeutic Interventions, Editor(s): S. Zahra Bathaie, Fuyuhiko Tamanoi, The Enzymes, Academic Press, Volume 37, 2015, Pages 43-72, ISSN 1874-6047, ISBN 9780128038765, https://doi.org/10.1016/bs.enz.2015.05.001.

[2]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Kaempferol increases thermal stress resistance and longevity

Shubhankar Kulkarni Feb 03, 2021

Kaempferol is a flavonol found in foods like apples, grapes, tomatoes, potatoes, onions, broccoli, Brussels sprouts, squash, cucumbers, lettuce, green beans, peaches, blackberries, raspberries, and spinach.      A study showed that 100 mM Kaempferol increased the survival of C. elegans by 10%, protected it from thermal stress, and suppressed the accumulation of intracellular inflammatory reactive oxygen species and an aging biomarker - lipofuscin.     

[1]https://en.wikipedia.org/wiki/Kaempferol#:~:text=Common%20foods%20that%20contain%20kaempferol,blackberries%2C%20raspberries%2C%20and%20spinach.

[2]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Catechin increases stress resistance and longevity

Shubhankar Kulkarni Feb 03, 2021

Catechins are present in plums, apples, peaches, strawberries, cherries, broad beans, lentils, green, black, and oolong teas, red wine, and cocoa.      Treatment with 200 mM of catechin increased the longevity of C. elegans by 14%. Catechin also increases resistance to oxidative and thermal stress and causes detoxification of the body.     

[1]Yusuf Yilmaz. Novel uses of catechins in foods, Trends in Food Science & Technology, Volume 17, Issue 2, 2006, Pages 64-71, ISSN 0924-2244, https://doi.org/10.1016/j.tifs.2005.10.005.

[2]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Icariin increases stress resistance and longevity

Shubhankar Kulkarni Feb 03, 2021

Icariin is a flavonol diglycoside that is extracted from plants of the Epimedium genus. Treatment with 45 mM of Icariin extended the mean lifespan of C. elegans by about 21%. Icariside II, the predominant bioactive form of Icariin in vivo, increased thermo and oxidative stress tolerance in C. elegans at the concentration of 20 mM, decreased the rate of locomotion decline in late adulthood, and extended the lifespan of C. elegans by 20%. It is suggested that the lifespan extension caused by icariside II is dependent on the insulin/ IGF-1 and DAF-2/FOXO signaling pathways since daf-16 and daf-2 mutants did not show the extension in lifespan upon icariside II treatment. Icariside II also has a potent protective ability against age-related diseases since it delayed the onset of paralysis mediated by polyQ and Ab(1–42) proteotoxicity in two C. elegans models of human proteotoxic diseases.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Butein is a sirtuin activator and it increases lifespan

Shubhankar Kulkarni Feb 03, 2021

Butein, a plant-derived tetrahydroxychalcone, is a sirtuin activator. Since sirtuins have been positively associated with lifespan extension, a study screened specifically to isolate sirtuin activators. Butein increased the lifespan of the yeast S. cerevisiae by 31% when treated with a concentration of 10 mM.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Resveratrol exerts anti-aging effects along with an increase in lifespan

Shubhankar Kulkarni Feb 03, 2021

Resveratrol is a stilbene present in various berries and nuts. In metazoans, resveratrol increased the lifespan by 56%. In vitro, resveratrol delayed the appearance of senescence markers and showed protective effects against oxidative damage towards DNA. In S. cerevisiae, resveratrol, at a concentration of 10 mM, stimulated sir2 activity, increased DNA stability, and extended lifespan by about 70%. An increase in the lifespan was also observed in wild-type adult worms upon resveratrol treatment. A concentration of 200 mM of resveratrol increased lifespan in flies by about 20%. In mice, resveratrol exerted protective effects against a high-calorie diet and increased their survival. It also restored normal insulin sensitivity, reduced the IGF-1 levels, and improved mitochondria number and function. There is also evidence suggesting that resveratrol exerts its anti-aging effects independently from the sirtuin pathway.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Epigallocatechin gallate increases stress resistance and longevity

Shubhankar Kulkarni Feb 03, 2021

Epigallocatechin gallate is a polyphenol found in green tea, most berries, kiwis, cherries, pears, peaches, apples, avocados, pecans, pistachios, and hazelnuts.     Administration of 220 mM epigallocatechin gallate increased the mean lifespan of C. elegans by about 10%, attenuated intracellular oxidative stress, and decreased the formation of lipofuscin. Another study showed that a lower concentration of epigallocatechin gallate only marginally increased the lifespan but it improved under heat and oxidative stress suggesting that proper management of physiological stress improves lifespan over and above that observed without any stress. Epigallocatechin gallate has been suggested in the prevention and therapy of skin photoaging since it inhibited the activation of matrix metalloproteinases and the destruction of collagen in UV-B irradiated human dermal fibroblasts.     

[1]https://www.healthline.com/nutrition/egcg-epigallocatechin-gallate#sources

[2]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Polyphenol tannic acid

Shubhankar Kulkarni Feb 08, 2021

Polyphenol tannic acid, at a concentration of 100 mM, induced potent life-prolonging properties, enhanced thermal stress resistance, and slightly increased oxidative stress resistance in C. elegans. It was suggested that tannic acid mimicked pathogenic stressors, probably by inducing a hormetic effect.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Sulforaphane

Brett M. Dec 06, 2020

Sulforaphanes are sulfur-containing glycosides that are found in several plant species like vegetables (i.e., broccoli, cabbage, Brussel sprouts) and have been found to have positive effects on the life- and healthspan     . 

Dose-response studies in Drosophilia revealed that lower doses of sulforaphane tended to increase their lifespan while higher doses tended to decrease it. Interestingly, this compound was found to suppress the genetic toxicity induced by hydrogen peroxide regardless of the dose used, displaying its cytoprotective properties. In addition, the positive effects of sulforaphane have been found to depend on the extent to which these flies experience oxidative stress, further implicating this physiological process in the role of aging      . 

In preclinical models of Alzheimer's induced by the aging accelerator, d-galactose, sulforaphane was found to mitigate the formation the aging-associated cognitive deficits, beta-amyloid plaques, carbonylated proteins, and desensitized antioxidant response      . Albeit, the administration of this glycoside occurred over the course of 80 days, so it would be interesting what sort of short-term effects this compound has on aging processes. 

Type 2 Diabetes is also associated with aging, and chronic treatment with sulforaphane (0.5 mg/kg for 3 months) was found to mitigate the complications that can arise following a diagnosis of diabetes, such as oxidative stress and inflammation characterized by VCAM-1 and TNF-alpha. Moreover, the antioxidant response was increased via Nrf2 mechanism and these effects were also found using different concentrations of broccoli extract      .

Taken together, sulforaphane seems to be a promising agent that can suppress many of the physiological abnormalities that can arise with the aging process.

[1]Fuentes F, Paredes-Gonzalez X, Kong AN (2015) Dietary glucosinolates sulforaphane, phenethyl isothiocyanate, indole-3-carbinol/3,30 -diindolylmethane: anti-oxidative stress/inflammation, Nrf2, epigenetics/epigenomics and in vivo cancer chemopreventive efficacy. Curr Pharmacol Rep 1:179–196. https://doi.org/10.1007/s40495-015-0017- y

[2]Villatoro-Pulido M, Font R, Saha S, Obrego´n-Cano S, Anter J, Mun˜oz-Serrano A, De Haro-Bailo´n A, Alonso-Moraga A, Del Rı´o-Celestino M (2012) In vivo biological activity of rocket extracts (Eruca vesicaria subsp. sativa (Miller) Thell) and sulforaphane. Food Chem Toxicol 50:1384–1392. https://doi.org/10.1016/j.fct.2012.02.017

[3]Zhang R, Zhang J, Fang L, Li X, Zhao Y, Shi W, An L (2015) Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer’s disease-like lesions. Int J Mol Sci 15:14396–14410. https://doi.org/10.3390/ ijms150814396

[4]Xu Z, Wang S, Ji H, Zhang Z, Chen J, Tan Y, Wintergerst K, Zheng Y, Sun J, Cai L (2016) Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice. Sci Rep 6:30252. https://doi.org/10. 1038/srep30252

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Caffeic acid increases lifespan and thermotolerance

Shubhankar Kulkarni Feb 10, 2021

Caffeic acid, found in apples, artichoke, berries, and pears, extended lifespan of C. elegans by about 11% and enhanced thermotolerance in C. elegans via its antioxidative properties at a concentration of 300 mM.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Rosmarinic acid extends lifespan and increases thermotolerance

Shubhankar Kulkarni Feb 10, 2021

Rosmarinic acid, found in culinary herbs such as basil, holy basil, lemon balm, rosemary, marjoram, sage, thyme, and peppermint, extended lifespan of C. elegans by about 11% and enhanced thermotolerance via their antioxidative properties at a concentration of 200 mM.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Gallic acid increases lifespan

Shubhankar Kulkarni Feb 10, 2021

Gallic acid, found in blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut, tea, and wine increased lifespan in C. elegans by about 10% at a concentration of 25 mM.    

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Ellagic acid increases lifespan

Shubhankar Kulkarni Feb 10, 2021

Ellagic acid, found in strawberries, raspberries, blackberries, cherries, and walnuts, increased lifespan in C. elegans by about 10% at a concentration of 800 mM.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Acteoside increases lifespan

Shubhankar Kulkarni Feb 10, 2021

About 0.64 to 2.56 mg/ mL of the herbal phenylethanoid glycoside acteoside in Drosophila culture medium increased their lifespan by 9 to 15%.      Acteoside is found in common verbena, lemon verbena, and olives.

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Tyrosol increases lifespan and resistance to thermal and oxidative stress.

Shubhankar Kulkarni Feb 10, 2021

Tyrosol is a phenylethanoid, mostly associated with olive oil. It increased the lifespan of C. elegans by about 11% at a concentration of 250 mM. The researchers suggest that this extension was mediated by an enhanced thermotolerance and resistance to oxidative stress. The extension caused no notable effects on the overall growth of the C. elegans. The components of the heat shock response (HSF-1) and the INS/IGF-1 and DAF-16/FOXO signalling are suggested to be involved in the process. Thus, the compound may act by promoting a hormetic effect.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

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Glaucarubinone increases lifespan and inhibits colorectal cancer growth

Shubhankar Kulkarni Feb 10, 2021

Glaucarubinone, a quassinoid found in Tree-of-Heaven, increased lifespan in C. elegans by about 80% at a concentration of 100 nM. Glaucarubinone also reduced the body fat content of C. elegans, suggesting that it may act through the nutrient sensing pathway.     Glaucarubinone was also found to inhibit colorectal cancer growth.     

[1]Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL. Natural compounds with anti-ageing activity. Nat Prod Rep. 2013 Oct 11;30(11):1412-37. doi: 10.1039/c3np70031c. PMID: 24056714.

[2]Huynh N, Beutler JA, Shulkes A, Baldwin GS, He H. Glaucarubinone inhibits colorectal cancer growth by suppression of hypoxia-inducible factor 1α and β-catenin via a p-21 activated kinase 1-dependent pathway. Biochim Biophys Acta. 2015 Jan;1853(1):157-65. doi: 10.1016/j.bbamcr.2014.10.013. Epub 2014 Oct 22. PMID: 25409929; PMCID: PMC7709143.

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How can we apply bioelectric signals in medicine and regeneration to facilitate longevity?

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How could we completely erase the epigenetic marks during cellular reprogramming?

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How can we determine whether pregnancy is beneficial or detrimental to the mother's health

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Curcumin Derived From Turmeric

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Flavonoids in Blueberries

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Biophenols from olives and nuts reduce cognitive decline and improve cardiovascular markers

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Natural compounds found in ginger extracts

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Astaxanthin as a neuroprotector

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Sargaquinoic acid from brown alga Sargassum sagamianum

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Rapamycin from Streptomyces hygroscopicus strain AY B994

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Quercetin increases stress resistance and longevity

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Kaempferol increases thermal stress resistance and longevity

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Catechin increases stress resistance and longevity

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Icariin increases stress resistance and longevity

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Butein is a sirtuin activator and it increases lifespan

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Resveratrol exerts anti-aging effects along with an increase in lifespan

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Epigallocatechin gallate increases stress resistance and longevity

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Polyphenol tannic acid

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Sulforaphane

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Caffeic acid increases lifespan and thermotolerance

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Rosmarinic acid extends lifespan and increases thermotolerance

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Gallic acid increases lifespan

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Ellagic acid increases lifespan

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Acteoside increases lifespan

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Tyrosol increases lifespan and resistance to thermal and oxidative stress.

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Glaucarubinone increases lifespan and inhibits colorectal cancer growth

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General comments

ByShubhankar Kulkarni

Treatment for Age-related Macular Degeneration

BySubash Chapagain

How can we apply bioelectric signals in medicine and regeneration to facilitate longevity?

ByDarko Savic

How can people contribute to humanity's quest for biological immortality?

ByShubhankar Kulkarni

How could we completely erase the epigenetic marks during cellular reprogramming?

ByDragan Otasevic

Can you conceptualize a meme that illustrates how Elon Musk is wrong for not supporting humanity's longevity efforts?

ByJamila

How can we determine whether pregnancy is beneficial or detrimental to the mother's health

ByShubhankar Kulkarni

Defining the aging phenotype

ByJamila

What methods can be used to control in vivo cellular reprogramming?

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