Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?

References

• Bardócz S, Duguid TJ, Brown DS, et al. The importance of dietary polyamines in cell regeneration and growth. Br J Nutr. 1995;73:819–828.
   PubMed Web of Science ®Google Scholar
• Igarashi K, Kashiwagi K. Modulation of cellular function by polyamines. Int J Biochem Cell Biol. 2010;42:39–51.
   PubMed Web of Science ®Google Scholar
• Pegg AE. Functions of Polyamines in Mammals. J Biol Chem. 2016;291:14904–14912.
   PubMed Web of Science ®Google Scholar
• Madeo F, Eisenberg T, Pietrocola F, et al. Spermidine in health and disease. Science. 2018;359(6374):eaan2788.
   PubMedGoogle Scholar
• Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22:1428–1438.
   PubMed Web of Science ®Google Scholar
• Eisenberg T, Büttner S, Kroemer G, et al. The mitochondrial pathway in yeast apoptosis. Apoptosis Int J Program Cell Death. 2007;12:1011–1023.
   PubMed Web of Science ®Google Scholar
• Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11:1305–1314.
   PubMed Web of Science ®Google Scholar
• Yue F, Li W, Zou J, et al. Spermidine prolongs lifespan and prevents liver fibrosis and hepatocellular carcinoma by activating MAP1S-mediated autophagy. Cancer Res. 2017;77:2938–2951.
   PubMed Web of Science ®Google Scholar
• Gupta VK, Scheunemann L, Eisenberg T, et al. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner. Nat Neurosci. 2013;16:1453–1460.
   PubMed Web of Science ®Google Scholar
• Wang I-F, Guo B-S, Liu Y-C, et al. Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci. 2012;109:15024–15029.
   PubMed Web of Science ®Google Scholar
• Yang Q, Zheng C, Cao J, et al. Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages. Cell Death Differ. 2016;23:1850–1861.
   PubMed Web of Science ®Google Scholar
• Pietrocola F, Pol J, Vacchelli E, et al. Caloric restriction mimetics enhance anticancer immunosurveillance. Cancer Cell. 2016;30:147–160.
   PubMed Web of Science ®Google Scholar
• Puleston DJ, Simon AK. New roles for autophagy and spermidine in T cells. Microb Cell. 2015;2:91–93.
   PubMed Web of Science ®Google Scholar
• Puleston DJ, Zhang H, Powell TJ, et al. Autophagy is a critical regulator of memory CD8(+) T cell formation. eLife. 2014;3:e03706. https://elifesciences.org/articles/03706
   Web of Science ®Google Scholar
• Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146:682–695.
   PubMed Web of Science ®Google Scholar
• Carmona-Gutierrez D, Hughes AL, Madeo F, et al. The crucial impact of lysosomes in aging and longevity. Ageing Res Rev. 2016;32:2–12.
   PubMed Web of Science ®Google Scholar
• Yin Z, Pascual C, Klionsky DJ. Autophagy: machinery and regulation. Microb Cell. 2016;3:588–596.
   PubMed Web of Science ®Google Scholar
• Frake RA, Ricketts T, Menzies FM, et al. Autophagy and neurodegeneration. J Clin Invest. 2015;125:65–74.
   PubMed Web of Science ®Google Scholar
• Choi AMK, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368:651–662.
   PubMed Web of Science ®Google Scholar
• Zhang C, Cuervo AM. Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med. 2008;14:959–965.
   PubMed Web of Science ®Google Scholar
• Pietrocola F, Lachkar S, Enot DP, et al. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015;22:509–516.
   PubMed Web of Science ®Google Scholar
• Mariño G, Pietrocola F, Eisenberg T, et al. Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol Cell. 2014;53:710–725.
   PubMed Web of Science ®Google Scholar
• Du Toit A, De Wet S, Hofmeyr J-HS, et al. The precision control of autophagic flux and vesicle dynamics—a micropattern approach. Cells. 2018;7:94.
   Web of Science ®Google Scholar
• Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392–395.
   PubMed Web of Science ®Google Scholar
• Neff F, Flores-Dominguez D, Ryan DP, et al. Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest. 2013;123:3272–3291.
   PubMed Web of Science ®Google Scholar
• Pucciarelli S, Moreschini B, Micozzi D, et al. Spermidine and spermine are enriched in whole blood of nona/centenarians. Rejuvenation Res. 2012;15:590–595.
   PubMed Web of Science ®Google Scholar
• Scalabrino G, Ferioli ME. Polyamines in mammalian ageing: an oncological problem, too? A review. Mech Ageing Dev. 1984;26:149–164.
   PubMed Web of Science ®Google Scholar
• Pegg AE. Mammalian polyamine metabolism and function. IUBMB Life. 2009;61:880–894.
   PubMed Web of Science ®Google Scholar
• Kee K, Foster BA, Merali S, et al. Activated polyamine catabolism depletes acetyl-CoA pools and suppresses prostate tumor growth in TRAMP mice. J Biol Chem. 2004;279:40076–40083.
   PubMed Web of Science ®Google Scholar
• Jell J, Merali S, Hensen ML, et al. Genetically altered expression of spermidine/spermine N1-acetyltransferase affects fat metabolism in mice via acetyl-CoA. J Biol Chem. 2007;282:8404–8413.
   PubMed Web of Science ®Google Scholar
• Hai Y, Shinsky SA, Porter NJ, et al. Histone deacetylase 10 structure and molecular function as a polyamine deacetylase. Nat Commun. 2017;8:15368.
   PubMed Web of Science ®Google Scholar
• Nowotarski SL, Woster PM, Casero RA. Polyamines and cancer: implications for chemotherapy and chemoprevention. Expert Rev Mol Med. 2013;15:e3.
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Kibe R, Ooga T, et al. Impact of intestinal microbiota on intestinal luminal metabolome. Sci Rep. 2012;2:233.
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Benno Y. The relationship between microbiota and polyamine concentration in the human intestine: a pilot study. Microbiol Immunol. 2007;51:25–35.
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Kurihara S, Kibe R, et al. Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production. PloS One. 2011;6:e23652.
   PubMed Web of Science ®Google Scholar
• Kibe R, Kurihara S, Sakai Y, et al. Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. Sci Rep. 2014;4:4548.
   PubMed Web of Science ®Google Scholar
• Milovic V. Polyamines in the gut lumen: bioavailability and biodistribution. Eur J Gastroenterol Hepatol. 2001;13:1021–1025.
   PubMed Web of Science ®Google Scholar
• Kiechl S, Pechlaner R, Willeit P, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018.
   PubMed Web of Science ®Google Scholar
• Soda K, Kano Y, Sakuragi M, et al. Long-term oral polyamine intake increases blood polyamine concentrations. J Nutr Sci Vitaminol (Tokyo). 2009;55:361–366.
   PubMed Web of Science ®Google Scholar
• Schwarz C, Stekovic S, Wirth M, et al. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. Aging. 2018;10:19–33.
   PubMedGoogle Scholar
• Pietrocola F, Demont Y, Castoldi F, et al. Metabolic effects of fasting on human and mouse blood in vivo. Autophagy. 2017;13:567–578.
   PubMed Web of Science ®Google Scholar