Stefan Kiechl1, Raimund Pechlaner1,2, Peter Willeit1,2,3, Marlene Notdurfter4, Bernhard Paulweber5, Karin Willeit1, Philipp Werner6, Christoph Ruckenstuhl7,8, Bernhard Iglseder5, Siegfried Weger4, Barbara Mairhofer4, Markus Gartner4, Ludmilla Kedenko5, Monika Chmelikova9, Slaven Stekovic7,8, Hermann Stuppner10,11, Friedrich Oberhollenzer4, Guido Kroemer12,13,14,15,16,17, Manuel Mayr2, Tobias Eisenberg7,8, Herbert Tilg18, Frank Madeo7,8, Johann Willeit1. 1. Departments of Neurology, Medical University of Innsbruck, Innsbruck, Austria. 2. King's British Heart Foundation Center, King's College London, London, United Kingdom. 3. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4. Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy. 5. First Department of Internal Medicine and Department of Geriatric Medicine, Paracelsus Medical University, Salzburg, Austria. 6. Department of Acute Neurology and Stroke, Feldkirch Academic Teaching Hospital, Feldkirch, Austria. 7. Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria. 8. BioTechMed Graz, Graz, Austria. 9. Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic. 10. Institute of Pharmacy/Pharmacognosy. 11. Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria. 12. Equipe 11 labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. 13. Cell Biology and Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France. 14. Institut national de la santé et de la recherche médicale, U1138, Paris, France. 15. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 16. Université Pierre et Marie Curie, Paris, France. 17. Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France. 18. Departments of Internal Medicine I, Gastroenterology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Abstract
Background: Spermidine administration is linked to increased survival in several animal models. Objective: The aim of this study was to test the potential association between spermidine content in diet and mortality in humans. Design: This prospective community-based cohort study included 829 participants aged 45-84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian-administered validated food-frequency questionnaires (2540 assessments) in 1995, 2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths occurred. Results: All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to 23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age-, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48 (95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41), respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001). Further adjustment for lifestyle factors, established predictors of mortality, and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001). The association was consistent in subgroups, robust against unmeasured confounding, and independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex-, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI: 0.53, 0.95; P = 0.019). The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-y (95% CI: 3.6, 8.1 y) younger age. Conclusion: Our findings lend epidemiologic support to the concept that nutrition rich in spermidine is linked to increased survival in humans. This trial was registered at www.clinicaltrials.gov as NCT03378843.
Background: Spermidine administration is linked to increased survival in several animal models. Objective: The aim of this study was to test the potential association between spermidine content in diet and mortality in humans. Design: This prospective community-based cohort study included 829 participants aged 45-84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian-administered validated food-frequency questionnaires (2540 assessments) in 1995, 2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths occurred. Results: All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to 23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age-, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48 (95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41), respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001). Further adjustment for lifestyle factors, established predictors of mortality, and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001). The association was consistent in subgroups, robust against unmeasured confounding, and independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex-, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI: 0.53, 0.95; P = 0.019). The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-y (95% CI: 3.6, 8.1 y) younger age. Conclusion: Our findings lend epidemiologic support to the concept that nutrition rich in spermidine is linked to increased survival in humans. This trial was registered at www.clinicaltrials.gov as NCT03378843.
Authors: Pratishtha Chatterjee; Anne M Fagan; Chengjie Xiong; Matthew McKay; Atul Bhatnagar; Yunqi Wu; Abhay K Singh; Kevin Taddei; Ian Martins; Samantha L Gardener; Mark P Molloy; Gerhard Multhaup; Colin L Masters; Peter R Schofield; Tammie L S Benzinger; John C Morris; Randall J Bateman; Steven M Greenberg; Marieke J H Wermer; Mark A van Buchem; Hamid R Sohrabi; Ralph N Martins Journal: J Alzheimers Dis Date: 2021 Impact factor: 4.472
Authors: Alain P Gobert; Yvonne L Latour; Mohammad Asim; Daniel P Barry; Margaret M Allaman; Jordan L Finley; Thaddeus M Smith; Kara M McNamara; Kshipra Singh; Johanna C Sierra; Alberto G Delgado; Paula B Luis; Claus Schneider; M Kay Washington; M Blanca Piazuelo; Shilin Zhao; Lori A Coburn; Keith T Wilson Journal: Gastroenterology Date: 2021-11-10 Impact factor: 22.682
Authors: Libia Alejandra García-Flores; Cara L Green; Sharon E Mitchell; Daniel E L Promislow; David Lusseau; Alex Douglas; John R Speakman Journal: Proc Natl Acad Sci U S A Date: 2021-08-03 Impact factor: 11.205