17 Spermidine Papers

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Abstract

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Date

Authors

LinkToPaper

Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)—study protocol for a randomized controlled trial

28

01 May 2019

Miranka Wirth, Claudia Schwarz, Gloria Benson, Nora Horn, Ralph Buchert, Catharina Lange, Theresa Köbe, Stefan Hetzer, Marta Maglione, Eva Michael, Stefanie Märschenz, Knut Mai, Ute Kopp, Dietmar Schmitz, Ulrike Grittner, Stephan J. Sigrist, Slaven Stekovic, Frank Madeo & Agnes Flöel

https://alzres.biomedcentral.com/articles/10.1186/s13195-019-0484-1

The positive effect of spermidine in older adults suffering from dementia

The worldwide prevalence of dementia is estimated at 35.6 million and will rise to 115 million by 2050. There is therefore an urgent need for well-founded dementia diagnostics and well-researched therapeutic options. Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. They also confirmed that nutritional intervention with the natural polyamine spermidine can prevent memory loss in aging model organisms. This multicentric double-blind preliminary study focused on the effect of oral spermidine supplementation on older adults’ cognitive performance. Memory tests were carried out on 85 subjects aged between 60 and 96 years in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration and measurement of metabolic parameters. The results demonstrated a clear correlation between the intake of spermidine and the improvement in cognitive performance in subjects with mild and moderate dementia in the group treated with the higher spermidine dosage. The most substantial improvement in test performance was found in the group of subjects with mild dementia with an increase of 2.23 points (p = 0.026) in the mini mental state examination (MMSE) and 1.99 (p = 0.47) in phonematic fluidity. By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.

1

19 November 2020

Thomas Pekar MA, Katharina Bruckner BSc, Susanne Pauschenwein-Frantsich, Anna Gschaider BSc, Martina Oppliger BSc, Julia Willesberger BSc, Petra Ungersbäck BSc, Aribert Wendzel MSc, Alexandra Kremer, Walter Flak, Felix Wantke & Reinhart Jarisch

https://link.springer.com/article/10.1007/s00508-020-01758-y

Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses

Aging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila. Here we demonstrate that dietary spermidine protects from age-related synaptic alterations at hippocampal mossy fiber (MF)-CA3 synapses and prevents the aging-induced loss of neuronal mitochondria. Dietary spermidine rescued age-dependent decreases in synaptic vesicle density and largely restored defective presynaptic MF-CA3 long-term potentiation (LTP) at MF-CA3 synapses (MF-CA3) in aged animals. In contrast, spermidine failed to protect CA3-CA1 hippocampal synapses characterized by postsynaptic LTP from age-related changes in function and morphology. Our data demonstrate that dietary spermidine attenuates age-associated deterioration of MF-CA3 synaptic transmission and plasticity. These findings provide a physiological and molecular basis for the future therapeutic usage of spermidine.

13

23 December 2019

Marta Maglione, Gaga Kochlamazashvili, Tobias Eisenberg, Bence Rácz, Eva Michael, David Toppe, Alexander Stumpf, Alexander Wirth, André Zeug, Franziska E. Müller, Laura Moreno-Velasquez, Rosanna P. Sammons, Sebastian J. Hofer, Frank Madeo, Tanja Maritzen, Nikolaus Maier, Evgeni Ponimaskin, Dietmar Schmitz, Volker Haucke & Stephan J. Sigrist

https://www.nature.com/articles/s41598-019-56133-3

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline

Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3-month randomized, placebo-controlled, double-blind Phase II trial was conducted with supplementation of the spermidine-rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo-treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self-reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

56

January 2018

Claudia Schwarz, Slaven Stekovic, Miranka Wirth, Gloria Benson, Philipp Royer, Stephan Sigrist, Thomas R Pieber, Christopher Dammbrueck, Christoph Magnes, Tobias Eisenberg, Tobias Pendl, Jens Bohlken, Theresa Köe, Frank Madeo, Agnes Flöel

https://www.researchgate.net/publication/322346958_Safety_and_tolerability_of_spermidine_supplementation_in_mice_and_older_adults_with_subjective_cognitive_decline

Spermidine in health and disease

Interventions that delay aging and protect from age-associated disease are slowly approaching clinical implementation. Such interventions include caloric restriction mimetics, which are defined as agents that mimic the beneficial effects of dietary restriction while limiting its detrimental effects. One such agent, the natural polyamine spermidine, has prominent cardioprotective and neuroprotective effects and stimulates anticancer immunosurveillance in rodent models. Moreover, dietary polyamine uptake correlates with reduced cardiovascular and cancer-related mortality in human epidemiological studies. Spermidine preserves mitochondrial function, exhibits anti-inflammatory properties, and prevents stem cell senescence. Mechanistically, it shares the molecular pathways engaged by other caloric restriction mimetics: It induces protein deacetylation and depends on functional autophagy. Because spermidine is already present in daily human nutrition, clinical trials aiming at increasing the uptake of this polyamine appear feasible.

329

January 2018

Frank Madeo, Tobias Eisenberg, Federico Pietrocola, Guido Kroemer

https://www.researchgate.net/publication/322706501_Spermidine_in_health_and_disease

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

Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels.

57

October 2018

Frank Madeo, Maria Anna Bauer, Didac Carmona-Gutierrez, Guido Kroemer

https://www.researchgate.net/publication/328247460_Spermidine_a_physiological_autophagy_inducer_acting_as_an_anti-aging_vitamin_in_humans

Spermidine: A novel autophagy inducer and longevity elixir

Spermidine is a ubiquitous polycation that is synthesized from putrescine and serves as a precursor of spermine. Putrescine, spermidine and spermine all are polyamines that participate in multiple known and unknown biological processes. Exogenous supply of spermidine prolongs the life span of several model organisms including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans) and flies (Drosophila melanogaster) and significantly reduces age-related oxidative protein damage in mice, indicating that this agent may act as a universal anti-aging drug. Spermidine induces autophagy in cultured yeast and mammalian cells, as well as in nematodes and flies. Genetic inactivation of genes essential for autophagy abolishes the life span-prolonging effect of spermidine in yeast, nematodes and flies. These findings complement expanding evidence that autophagy mediates cytoprotection against a variety of noxious agents and can confer longevity when induced at the whole-organism level. We hypothesize that increased autophagic turnover of cytoplasmic organelles or long-lived proteins is involved in most if not all life span-prolonging therapies.

122

January 2010

Frank Madeo, Tobias Eisenberg, Sabrina Büttner, Christoph Ruckenstuhl, Guido Kroemer

https://www.researchgate.net/publication/41174078_Spermidine_A_novel_autophagy_inducer_and_longevity_elixir

Higher spermidine intake is linked to lower mortality: A prospective population-based study

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 http://www.clinicaltrials.gov as NCT03378843.

97

June 2018

Stefan Kiechl, Raimund Pechlaner, Peter Willeit, Marlene Notdurfter, Bernhard Paulweber, Karin Willeit, Philipp Werner, Christoph Ruckenstuhl, Bernhard Iglseder, Siegfried Weger, Azienda Sanitaria dell'Alto Adige, Barbara Mairhofer, Markus Gartner, Ludmilla Kedenko, Monika Chmelikova, Slaven Stekovic, Hermann Stuppner, Friedrich Oberhollenzer, Guido Kroemer, Manuel Mayr, Tobias Eisenberg, Herbert Tilg, Frank Madeo, Johann Willeit

https://www.researchgate.net/publication/326089081_Higher_spermidine_intake_is_linked_to_lower_mortality_A_prospective_population-based_study

The Function of Spermine

Polyamines play important roles in cell physiology including effects on the structure of cellular macromolecules, gene expression, protein function, nucleic acid and protein synthesis, regulation of ion channels, and providing protection from oxidative damage. Vertebrates contain two polyamines, spermidine and spermine, as well as their precursor, the diamine putrescine. Although spermidine has an essential and unique role as the precursor of hypusine a post-translational modification of the elongation factor eIF5A, which is necessary for this protein to function in protein synthesis, no unique role for spermine has been identified unequivocally. The existence of a discrete spermine synthase enzyme that converts spermidine to spermine suggest that spermine must be needed and this is confirmed by studies with Gy mice and human patients with Snyder-Robinson syndrome in which spermine synthase is absent or greatly reduced. In both cases, this leads to a severe phenotype with multiple effects among which are intellectual disability, other neurological changes, hypotonia, and reduced growth of muscle and bone. This review describes these alterations and focuses on the roles of spermine which may contribute to these phenotypes including reducing damage due to reactive oxygen species, protection from stress, permitting correct current flow through inwardly rectifying K(+) channels, controlling activity of brain glutamate receptors involved in learning and memory, and affecting growth responses. Additional possibilities include acting as storage reservoir for maintaining appropriate levels of free spermidine and a possible non-catalytic role for spermine synthase protein. © 2014 IUBMB Life, 2014.

105

February 2014

Anthony Pegg

https://www.researchgate.net/publication/259608044_The_Function_of_Spermine

Spermidine as a target for cancer therapy

Spermidine, as a natural component from polyamine members, is originally isolated from semen and also existed in many natural plants, and can be responsible for cell growth and development in eukaryotes. The supplementation of spermidine can extend health and lifespan across species. Although the elevated levels of polyamines and the regulation of rate-limiting enzymes for polyamine metabolism have been identified as the biomarkers in many cancers, recent epidemiological data support that an increased uptake of spermidine as a caloric restriction mimic can reduce overall mortality associated with cancers. The possible mechanisms between spermidine and cancer development may be related to the precise regulation of polyamine metabolism, anti-cancer immunosurveillance, autophagy, and apoptosis. Increased intake of polyamine seems to suppress tumorigenesis, but appears to accelerate the growth of established tumors. Based on these observations and the absolute requirement for polyamines in tumor growth, spermidine could be a rational target for chemoprevention and clinical therapeutics of cancers.

9

May 2020

Jingjing Fan, Ziyuan Feng, Ning Chen

https://www.researchgate.net/publication/341613241_Spermidine_as_a_target_for_cancer_therapy

Studies of the mechanism by which increased spermidine/spermine N1-acetyltransferase activity increases susceptibility to skin carcinogenesis

Previous studies have shown that keratin 6 (K6)-spermidine/spermine N1-acetyltransferase (SSAT) transgenic mice, which modestly over-express SSAT in the skin, are more sensitive to tumor induction by a two-stage tumorigenesis protocol using initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). To evaluate the role of altered levels of polyamines and oxidative stress in this increase, studies were carried out with pharmacologic and genetic manipulation of K6-SSAT mice subjected to DMBA/TPA carcinogenesis. The increased tumor incidence was partially prevented by treatment with 1,4-bis-[N-(buta-2,3-dienyl)amino]butane, an inhibitor of acetylpolyamine oxidase which prevented degradation of the acetylated polyamines. This result suggests that toxic products such as reactive oxygen species and aldehydes liberated by the action of polyamine oxidase on the acetylated polyamines formed by SSAT may enhance tumor development. Breeding of the K6-SSAT mice with K6-antizyme (AZ) mice [which express AZ, a negative regulator of ornithine decarboxylase (ODC)] blocked the development of tumors. In addition, treatment of tumor-bearing K6-SSAT mice with the ODC inhibitor, alpha-difluoromethylornithine, resulted in the complete regression of established tumors. In contrast, treatment with N1,N11-bis(ethyl)norspermidine which increased SSAT activity in the tumors did not enhance regression. These results indicate that the tumor progression in K6-SSAT mice is dependent on elevated ODC activity and increased putrescine levels and may be further enhanced by oxidative stress. They support the use of strategies to modulate polyamine levels through the inhibition of ODC activity or polyamine uptake, but not via increased SSAT expression, for cancer chemoprevention in individuals at high risk for skin tumor development.

36

December 2007

Xiaojing Wang, David J Feith, Pat Welsh, Catherine S Coleman, Christina Lopez, Patrick M. Woster, Thomas G O'Brien, Anthony Pegg

https://www.researchgate.net/publication/6164729_Studies_of_the_mechanism_by_which_increased_spermidinespermine_N1-acetyltransferase_activity_increases_susceptibility_to_skin_carcinogenesis

Spermine and spermidine are cytotoxic towards intestinal cell cultures, but are they a health hazard at concentrations found in foods?

Spermine and spermidine are polyamines (PA) naturally present in all organisms, in which they have important physiological functions. However, an excess of PA has been associated with health risks. PA accumulates at quite high concentrations in some foods, but a quantitative assessment of the risk they pose has been lacking. In the present work, the cytotoxicity of spermine and spermidine was evaluated using an in vitro human intestinal cell model, and employing real-time cell analysis. Both spermine and spermidine showed a dose-dependent cytotoxic effect towards the cultured cells, with necrosis the mode of action of spermidine and perhaps also that of spermine. Spermine was more cytotoxic than spermidine, but for both PA the concentrations found to be toxic were above the maximum at which they have been found in food. The present results do not, therefore, support the idea that spermine or spermidine in food is harmful to healthy people.

14

July 2018

Beatriz del Rio, Begoña Redruello, Daniel M. Linares, Victor Ladero, Patricia Ruas-Madiedo, María Fernández, M. Cruz Martín, Miguel A Alvarez

https://www.researchgate.net/publication/326124848_Spermine_and_spermidine_are_cytotoxic_towards_intestinal_cell_cultures_but_are_they_a_health_hazard_at_concentrations_found_in_foods

Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery

Delirium is a marker of brain vulnerability, associated with increasing age, pre-existing cognitive impairment and, recently, cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease. This nested case-control study used a targeted quantitative metabolomic methodology to profile the preoperative CSF of patients (n = 54) who developed delirium following arthroplasty (n = 28) and those who did not (n = 26). The aim was to identify novel preoperative markers of delirium, and to assess potential correlations with clinical data. Participants without a diagnosis of dementia (≥65 years) undergoing elective primary hip or knee arthroplasty were postoperatively assessed for delirium once-daily for three days. Groups were compared using multivariate, univariate and receiving operator characteristic (ROC) methods. Multivariate modelling using Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) of metabolomic data readily distinguished between delirium and control groups (R2 ≤ 0.56; Q2 ≤ 0.10). Three metabolites (spermidine, putrescine and glutamine) significantly differed between groups (P < 0.05; FDR < 0.07), and performed well as CSF biomarkers (ROC > 0.75). The biomarker performance of the two polyamines (spermidine/putrescine) was enhanced by ratio with CSF Aβ42 (ROC > 0.8), and spermidine significantly correlated with Aβ42 (pearson r = −0.32; P = 0.018). These findings suggest that spermidine and putrescine levels could be useful markers of postoperative delirium risk, particularly when combined with Aβ42, and this requires further investigation.

9

March 2019

Xiaobei Pan, Emma L. CunninghamAnthony P. Passmore, Bernadette Mcguinness, Daniel F. McAuley, David Beverland, Seamus O'Brien, Tim Mawhinney, Jonathan M. Schott, Henrik Zetterberg, Brian D Green

https://www.researchgate.net/publication/331678195_Cerebrospinal_Fluid_Spermidine_Glutamine_and_Putrescine_Predict_Postoperative_Delirium_Following_Elective_Orthopaedic_Surgery

Spermidine is indispensable in differentiation of 3T3-L1 fibroblasts to adipocytes

Impaired adipogenesis has been shown to predispose to disturbed adipocyte function and development of metabolic abnormalities. Previous studies indicate that polyamines are essential in the adipogenesis in 3T3-L1 fibroblasts. However, the specific roles of individual polyamines during adipogenesis have remained ambiguous as the natural polyamines are readily interconvertible inside the cells. Here, we have defined the roles of spermidine and spermine in adipogenesis of 3T3-L1 cells by using (S')- and (R')- isomers of alpha-methylspermidine and (S,S')-, (R,S)- and (R,R')-diastereomers of alpha,omega-bismethylspermine. Polyamine depletion caused by alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, prevented adipocyte differentiation by suppressing the expression of its key regulators, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha. Adipogenesis was restored by supplementation of methylspermidine isomers but not of bismethylspermine diastereomers. Although both spermidine analogues supported adipocyte differentiation only (S)-methylspermidine was able to fully support cell growth after extended treatment with alpha-DFMO. The distinction between the spermidine analogues in maintaining growth was found to be in their different capability to maintain functional hypusine synthesis. However, the differential ability of spermidine analogues to support hypusine synthesis did not correlate with their ability to support differentiation. Our results show that spermidine, but not spermine, is essential for adipogenesis and that the requirement of spermidine for adipogenesis is not strictly associated with hypusine modification. The involvement of polyamines in the regulation of adipogenesis may offer a potential application for the treatment of dysfunctional adipocytes in patients with obesity and metabolic syndrome.

33

July 2009

Susanna Vuohelainen, Eija Pirinen, Marc Cerrada-Gimenez, Tuomo A. Keinänen, Anne Uimari, Marko Pietilä, Alex R Khomutov, Russian Academy of Sciences, Juhani Jänne, Leena Alhonen

https://www.researchgate.net/publication/26303339_Spermidine_is_indispensable_in_differentiation_of_3T3-L1_fibroblasts_to_adipocytes

Comparative study on the effects of putrescine and spermidine pre-treatment on cadmium stress in wheat

In several cases a correlation was found between polyamines and abiotic stress tolerance. However, the individual polyamines may have different effects, which also vary depending on the type of treatment. When applied as seed soaking or added hydroponically 0.5 mM putrescine and spermidine, different changes were induced during 50 µM cadmium stress in wheat plants. Seed-soaked plants were exposed to cadmium immediately after germination for 5 days, while plants pre-treated with polyamines hydroponically were stressed at age of 14 days for 7 days. Putrescine pre-treatment was beneficial both as seed soaking and applied hydroponically, while spermidine only had a protective effect in the case of seed soaking, enhancing the Cd-induced oxidative stress when were pre-treated hydroponically. The differences observed were related to the polyamine metabolism. The accumulation of endogenous putrescine beyond a certain amount may be in relation with the negative effect of hy-droponic spermidine pre-treatment during Cd stress. The increased putrescine content was also correlated with the highest accumulation of Cd, salicylic acid and proline contents in plants treated with a combination of spermidine and Cd. However, the expression level of the gene encoding phytochelatin synthase was only influenced by hydroponically applied spermidine, which decreased it under cadmium stress. Changes in the activities of antioxidant enzymes, diamine and polyamine oxidases were also discussed.

39

October 2017

Judit Tajti, Tibor Janda, Imre Majláth, Gabriella Szalai, Magda Pál

https://www.researchgate.net/publication/320946326_Comparative_study_on_the_effects_of_putrescine_and_spermidine_pre-treatment_on_cadmium_stress_in_wheat

MAGHEMITE PARTICLES FOR SPERMIDINE SEPARATION

10

January 2020

Pavel Kopel, Natalia Cernei, Pavel Horky, Zuzana Lacková, Vedran Milosavljevic, Milica Gagic, Ondrej Zitka, Vojtech Adam

https://www.researchgate.net/publication/340160172_MAGHEMITE_PARTICLES_FOR_SPERMIDINE_SEPARATION

Nutritional Aspects of Spermidine

Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type–specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines.

7

August 2020

Frank Madeo, Sebastian J. Hofer, Tobias Pendl, Maria Anna Bauer, Tobias Eisenberg, Didac Carmona-Gutierrez, Guido Kroemer

https://www.researchgate.net/publication/342760810_Nutritional_Aspects_of_Spermidine

Spermidine delays aging in humans

External supply of the natural polyamine spermidine can extend life span in model organisms including yeast, nematodes, flies and mice. Recent epidemiological evidence suggests that increased uptake of spermidine with food also reduces overall, cardio-vascular and cancer-related mortality in humans. Here, we discuss the possible mechanisms of this intriguing spermidine effect. Polyamines including spermidine play an essential role in intermediate metabolism. Since they are synthesized by higher eukaryotic cells, they are not vitamins. How-ever, the levels of polyamines are profoundly influenced by their external supply, either by oral ingestion with different food items or by the intestinal microbiota that can synthesize polyamines as well

40

August 2018

Frank Madeo, Didac Carmona-Gutierrez, Oliver Kepp, Guido Kroemer

https://www.researchgate.net/publication/326876516_Spermidine_delays_aging_in_humans