Wired to be Weird

Ian McLaughlin | @_Anthropoid

Fountains of Youth? Metformin, Nicotinamide Riboside & Mononucleotide, Elysium & ChromaDex, & Caloric Restriction

Lucas Cranach - Der Jungbrunnen (The Fountain of Youth), 1564 (Wikimedia Commons)

Lucas Cranach - Der Jungbrunnen (The Fountain of Youth), 1564 (Wikimedia Commons)

Bo and I discuss some of the leading candidates for extending both human lifespan and “health-span”, including metformin, nicotinamide riboside & nicotinamide mononucleotide, and caloric restriction. We also chat about some of the companies working in this area, as well as novel business models that may or may not be a strategy to enable rigorous research of something as difficult to study as human lifespan.


Longevity References


1.      Bridgeman SC, Ellison GC, Melton PE, Newsholme P, Mamotte CDS. Epigenetic effects of metformin: From molecular mechanisms to clinical implications. Diabetes Obes Metab. 2018 Jul;20(7):1553-1562. doi: 10.1111/dom.13262. Epub 2018 Mar 22. Review. PubMed PMID: 29457866.

2.      Qian M, Liu B. Pharmaceutical Intervention of Aging. Adv Exp Med Biol. 2018;1086:235-254. doi: 10.1007/978-981-13-1117-8_15. PubMed PMID: 30232763.

3.      Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14. Review. PubMed PMID: 29249689; PubMed Central PMCID: PMC5842119.

4.      2017 Karen Weintraub, Medium - The life extension death match: https://medium.com/neodotlife/elysium-and-basis-vs-chromadex-and-tru-niagen-10264fca0bdb

5.      2018 Karen Weintraub, Medium - More on the supposed youth pill (NR): https://medium.com/neodotlife/nr-chromadex-niagen-elysium-basis-blood-pressure-study-cd1b383ccea

6.      2017 Karen Weintraub, MIT Technology Review - Critics Blast Star-Studded Advisory Board of Anti-Aging Company: https://www.technologyreview.com/s/603199/critics-blast-star-studded-advisory-board-of-anti-aging-company/

7.      2019 Alzforum - In small trial, EH301 (Elysium's Basis) Appears to Halt Progression of ALS: https://www.alzforum.org/news/research-news/small-trial-eh301-appears-halt-progression-als

8.      2019 Feb 17 - Marisa Taylor, Kaiser Health News - A pill to reverse aging; Enthusiasm outpaces reality: https://www.nbcnews.com/health/health-news/pill-reverse-aging-enthusiasm-outpaces-reality-n971616

9.      2016 Sarah Zhang, WIRED – The Weird Business Behind A Trendy “Anti-Aging” Pill: https://www.wired.com/2016/07/confused-elysiums-anti-aging-drug-yeah-fda/

10.   Konopka AR, Miller BF. Taming expectations of metformin as a treatment to extend healthspan. Geroscience. 2019 Feb 12;. doi: 10.1007/s11357-019-00057-3. [Epub ahead of print] Review. PubMed PMID: 30746605.

11.   Piskovatska V, Stefanyshyn N, Storey KB, Vaiserman AM, Lushchak O. Metformin as a geroprotector: experimental and clinical evidence. Biogerontology. 2019 Feb;20(1):33-48. doi: 10.1007/s10522-018-9773-5. Epub 2018 Sep 25. Review. PubMed PMID: 30255224.

12.   Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505. PubMed PMID: 11602624; PubMed Central PMCID: PMC209533.

13.   Witters LA. The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7. doi: 10.1172/JCI14178. Review. PubMed PMID: 11602616; PubMed Central PMCID: PMC209536.

14.   Stein LR, Imai S. The dynamic regulation of NAD metabolism in mitochondria. Trends Endocrinol Metab. 2012 Sep;23(9):420-8. doi: 10.1016/j.tem.2012.06.005. Epub 2012 Jul 21. PubMed PMID: 22819213; PubMed Central PMCID: PMC3683958.

15.   Aravinthan A. Cellular senescence: a hitchhiker's guide. Hum Cell. 2015 Apr;28(2):51-64. doi: 10.1007/s13577-015-0110-x. Epub 2015 Feb 18. Review. PubMed PMID: 25690721.

16.   2015 David Stipp, Scientific American Guest Blog - Beyond Resveratrol: The Anti-Aging NAD Fad: https://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad/

17.   2015 Jessica Leber, Fast Company - One Of The World’s Top Aging Researchers Has A Pill To Keep You Feeling Young: https://www.fastcompany.com/3041800/one-of-the-worlds-top-aging-researchers-has-a-pill-to-keep-you-feeling-young

18.   2015 Karen Weintraub, MIT Technology Review - The Anti-Aging Pill: https://www.technologyreview.com/s/534636/the-anti-aging-pill/

19.   2015 Stefanie Friedhoff, Boston Globe - Five Nobel laureates backing antiaging dietary supplement: https://www.bostonglobe.com/business/2015/02/03/anti-aging-supplement-from-prominent-local-scientists/FvHsy28Hd9fILmrR4OZArO/story.html

20.   Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016 Jun 14;23(6):1060-1065. doi: 10.1016/j.cmet.2016.05.011. Review. PubMed PMID: 27304507; PubMed Central PMCID: PMC5943638.

21.   2017 Marina N. Bolotnikova, Harvard Magazine – Anti-Aging Approaches: https://www.harvardmagazine.com/2017/09/anti-aging-breakthrough

22.    Bridgeman SC, Ellison GC, Melton PE, Newsholme P, Mamotte CDS. Epigenetic effects of metformin: From molecular mechanisms to clinical implications. Diabetes Obes Metab. 2018 Jul;20(7):1553-1562. doi: 10.1111/dom.13262. Epub 2018 Mar 22. Review. PubMed PMID: 29457866.

23.   Semba RD, Ferrucci L, Bartali B, Urpí-Sarda M, Zamora-Ros R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C. Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med. 2014 Jul;174(7):1077-84. doi: 10.1001/jamainternmed.2014.1582. PubMed PMID: 24819981; PubMed Central PMCID: PMC4346286.

24.   Campbell JM, Bellman SM, Stephenson MD, Lisy K. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Ageing Res Rev. 2017 Nov;40:31-44. doi: 10.1016/j.arr.2017.08.003. Epub 2017 Aug 10. Review. PubMed PMID: 28802803.

25.   2017 Jeffrey S. Flier, Boston Globe – Dietary supplements: Nobel or ignoble: https://www.bostonglobe.com/opinion/2017/03/30/dietary-supplements-nobel-ignoble/e5E6Cklw3RxlExEtGJe6mL/story.html

26.   Romero R, Erez O, Hüttemann M, Maymon E, Panaitescu B, Conde-Agudelo A, Pacora P, Yoon BH, Grossman LI. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. 2017 Sep;217(3):282-302. doi: 10.1016/j.ajog.2017.06.003. Epub 2017 Jun 12. Review. PubMed PMID: 28619690; PubMed Central PMCID: PMC6084482.

27.   Cuyàs E, Verdura S, Llorach-Parés L, Fernández-Arroyo S, Joven J, Martin-Castillo B, Bosch-Barrera J, Brunet J, Nonell-Canals A, Sanchez-Martinez M, Menendez JA. Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation. Front Endocrinol (Lausanne). 2018;9:657. doi: 10.3389/fendo.2018.00657. eCollection 2018. PubMed PMID: 30459716; PubMed Central PMCID: PMC6232372.

28.   Cuyàs E, Fernández-Arroyo S, Verdura S, García RÁ, Stursa J, Werner L, Blanco-González E, Montes-Bayón M, Joven J, Viollet B, Neuzil J, Menendez JA. Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism. Oncogene. 2018 Feb 15;37(7):963-970. doi: 10.1038/onc.2017.367. Epub 2017 Oct 23. PubMed PMID: 29059169.

29.   2018 Grand View Research - Dietary Supplements Market Size Worth $278.02 Billion By 2024: https://www.grandviewresearch.com/press-release/global-dietary-supplements-market

30.   2018 Johns Hopkins Bloomberg School of Public Health - Cost of Clinical Trials for New Drug FDA Approval Are Fraction of Total Tab: https://www.jhsph.edu/news/news-releases/2018/cost-of-clinical-trials-for-new-drug-FDA-approval-are-fraction-of-total-tab.html

31.   Klimova B, Novotny M, Kuca K. Anti-Aging Drugs - Prospect of Longer Life?. Curr Med Chem. 2018;25(17):1946-1953. doi: 10.2174/0929867325666171129215251. Review. PubMed PMID: 29189123.

32.   Li YR, Li S, Lin CC. Effect of resveratrol and pterostilbene on aging and longevity. Biofactors. 2018 Jan;44(1):69-82. doi: 10.1002/biof.1400. Epub 2017 Dec 6. Review. PubMed PMID: 29210129.

33.   Mitchell SJ, Bernier M, Aon MA, Cortassa S, Kim EY, Fang EF, Palacios HH, Ali A, Navas-Enamorado I, Di Francesco A, Kaiser TA, Waltz TB, Zhang N, Ellis JL, Elliott PJ, Frederick DW, Bohr VA, Schmidt MS, Brenner C, Sinclair DA, Sauve AA, Baur JA, de Cabo R. Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice. Cell Metab. 2018 Mar 6;27(3):667-676.e4. doi: 10.1016/j.cmet.2018.02.001. PubMed PMID: 29514072; PubMed Central PMCID: PMC5854409.

34.   Lee SH, Lee JH, Lee HY, Min KJ. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019 Jan;52(1):24-34. Review. PubMed PMID: 30526767; PubMed Central PMCID: PMC6386230.

NeuroByte - IQ & Psychiatry + A Cause of Dyslexia


A discussion of a study at least partly monitored by one of Ian's college mentors that explored whether there might be a relationship between high IQ scores and psychiatric & physiological diagnoses. We then discuss a study that blew Ian's mind, showing that some cases of dyslexia may be attributable to some unique structures within the eyes. 


1. Karpinski, R, Kolb, A, Tetrault, N, Borowski, T. High intelligence: A risk factor for psychological and physiological overexcitabilities. Intelligence. 2018 Jan;66:8-23. https://doi.org/10.1016/j.intell.2017.09.001. 

2. Le Floch A, Ropars G. Left-right asymmetry of the Maxwell spot centroids in adults without and with dyslexia. Proc Biol Sci. 2017 Oct 25;284(1865). pii: 20171380. doi: 10.1098/rspb.2017.1380. PubMed PMID: 29046375; PubMed Central PMCID: PMC5666095

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