Research Summary on Spermidine

Effects on Heart Health and Longevity

Spermidine (Spd), a polyamine, has been shown to improve heart health and longevity through mechanisms such as autophagy, mitophagy, and improved mitochondrial respiration. It enhances the mechanical properties of cardiomyocytes and is believed to be taken up by these cells, though the entry mechanism is yet to be fully understood.

Role in Intestinal Health

Spermidine is critical for hypusine formation, which is important for protein synthesis and intestinal health. Lower levels of the enzyme required for hypusine production are found in individuals with inflammatory bowel diseases. Hypusination is vital for normal intestinal function, and its deficiency can lead to increased cell proliferation, inflammation, and colon cancer.

Therapeutic Potential in Liver Fibrosis

Low spermidine levels are associated with advanced steatohepatitis. Spermidine supplementation has shown promise in treating liver fibrosis by decreasing extracellular matrix proteins, improving fibrosis, and inhibiting the activation of hepatic stellate cells.

Autophagy and Lifespan Extension

Spermidine and resveratrol can induce autophagy, which is protective and can extend lifespan in various organisms, including yeast, nematodes, flies, and human cells. These effects are linked to modulating acetylation processes within the cell.

Association with Brain Aging

Higher plasma levels of spermidine are associated with markers of brain aging such as reduced hippocampal volume and increased Alzheimer's disease score. Elevated spermidine levels could be early biomarkers for Alzheimer's disease and vascular brain pathology.

Dietary Intake and Health

Higher dietary intake of spermidine could reduce mortality, particularly from cardiovascular diseases and cancer. Spermidine supplementation has been shown to counteract the effects of aging.

Effects on Acute Pancreatitis

Spermidine has therapeutic potential in treating acute pancreatitis by targeting acetylcholinesterase and the serotonin transporter, reducing cell necrosis and inflammation.

Memory Improvement in Aging

Spermidine can counteract memory decline in aging fruit flies by inducing autophagy. It has potential as a treatment for memory loss associated with aging.

Role in Oocyte Quality and Female Reproductive Aging

Spermidine supplementation improves oocyte quality and reproductive outcomes in aged mice by enhancing mitophagy and mitochondrial function.

Prevention of Colitis and Colorectal Cancer

Spermidine supplementation improves colitis and prevents colon cancer by helping regulate colitis, inhibiting tumor development, and modulating the gut microbiome.

Cardiac Aging and Mitochondrial Function

Spermidine supplementation protects against cardiac aging by restoring polyamine levels and activating pathways that promote mitochondrial biogenesis and function.

Impact of Nutrition on Lifespan

Certain nutritional approaches, such as caloric restriction, methionine restriction, lower protein intake, or spermidine supplementation, can extend lifespan. Diets rich in whole grains, vegetables, nuts, and coffee are linked to a lower risk of all-cause mortality.

Protective Effects on Endurance Athletes

A mixture containing spermidine and other natural substances can reduce oxidative stress and muscle injury in athletes, suggesting benefits for muscle recovery.

Supplementation in Hypertension

A mixture including spermidine did not influence blood pressure levels but reduced oxidative stress and stimulated autophagy, potentially beneficial for preventing cardiovascular damage associated with hypertension.

Dementia Diagnostics and Treatments

Oral spermidine supplementation has shown cognitive improvement in older adults with mild to moderate dementia, with high doses associated with increased cognitive performance.

Ovarian Function Protection

Spermidine supplementation can improve ovarian endocrine function and reproductive capacity in mice affected by oxidative stress, suggesting its potential as a novel approach for protecting against ovarian damage.

Protective Effects on the Liver

Spermidine induces a nontraditional pathway involving NRF2, a critical transcription factor for cellular protection, by way of the protein MAP1S, offering liver protection against diseases like fibrosis.

Cardioprotective Agent in Diets

Spermidine serves as a heart-protective agent, enhancing cardiac autophagy and reducing blood pressure. It is associated with a lower risk of cardiovascular diseases.

Immune Function Enhancement

Spermidine supplementation restores autophagy pathway and improves the immune response of aged human B cells, suggesting potential to counteract immune senescence.

Therapeutic Potential for Brain Disorders

Spermidine shows promise in treating brain diseases, extending lifespan, and improving mitochondrial function by promoting autophagy.

Proangiogenic Effects in Aging

Spermidine supplementation has proangiogenic effects, improving the formation of new blood vessels and blood flow in aged mice, with potential treatment for ischemic conditions.

Oxidative Stress Reduction in Aging Mice

Spermidine supplementation reduces oxidative stress in aging mice, extending lifespan and preventing necrotic cell death through autophagy.

Anti-Aging Effects and Autophagy Promotion

Spermidine promotes autophagy, which impacts aging by reducing inflammation, altering lipid metabolism, and influencing cell growth, with the MAPK pathway being a key route for these effects.

Cardiovascular Protection and Heart Function Preservation

Oral spermidine supplementation can extend the lifespan of mice, protect against cardiovascular diseases, reduce heart inflammation, and preserve heart function.

Collagen-Related Muscle Disorders Treatment

Long-term spermidine treatment improves muscle strength, mitochondrial health, and neuromuscular junction integrity in mice with inherited muscle disorders.

Traumatic Brain Injury and Polyamine Catabolism

Changes in polyamine catabolism following traumatic brain injury in rats could lead to a loss of homeostasis in this pathway, suggesting potential treatments involving polyamine supplementation or inhibition of their oxidation.

Impact of Polyamine Intake on DNA Methylation

Increased consumption of polyamines, such as spermine, can reduce age-related DNA methylation errors and extend lifespan in mice, affecting gene methylation enzymes.

Neuroprotective Effects on Mitochondrial Dysfunction

Spermidine improves mitochondrial functions and corrects mitophagy impairments caused by mutant tau protein, indicating potential to counteract tau-related neurodegenerative diseases.

Protection Against Kidney Ischemia and Reperfusion Injury

Spermidine supplementation reduces plasma creatinine levels and tubular injury after kidney ischemia and reperfusion injury, suggesting protective effects against oxidative stress and necrosis.

Memory Performance Improvement in Dementia

Long-term spermidine supplementation shows improvement in memory performance in older adults with dementia, supporting its beneficial impact on cognitive function.

Reduction of Vascular Calcification

Spermidine reduces mineral deposits and calcification in vascular smooth muscle cells and arterial rings, linked to activation of the SIRT1 signaling pathway and reduction in endoplasmic reticulum stress.

Autophagy and Immune Senescence Counteraction

Spermidine modulates autophagy and counteracts immune senescence through the regulation of protein synthesis, with implications for immune system rejuvenation.

Role in Musculoskeletal Diseases

Polyamines like spermidine regulate autophagy naturally and possess anti-aging effects, suggesting potential therapeutic effects in musculoskeletal diseases characterized by muscle atrophy.

Ovarian Aging and Disease

Polyamines support cell growth and development, alleviating ovarian aging and participating in hormone synthesis and cell death regulation. However, excessive levels can contribute to ovarian disease.

Cardiac Mitochondrial Function in Aging

Spermidine supplementation may restore the number of mitochondria and improve their 3D structure in aged hearts, contributing to mitochondrial function and countering aging effects.

Link Between Mitochondrial Function, Brain Aging, and Spermidine

Spermidine promotes mitochondrial respiration and delays brain aging by donating a group required for the hypusination of eIF5A, maintaining mitochondrial health and preventing premature brain aging.

Spermidine and Obesity

Spermidine supplementation shows negative correlation with obesity, leading to weight loss and improved insulin resistance, potentially through enhanced gut health and microbiota function.

Cognitive Function and Dietary Spermidine

Dietary spermidine can improve cognitive function by enhancing hippocampal function and mitochondrial activity, with autophagy playing a key role.

Neuroprotection in Aging Rats

Spermidine supplementation reduces oxidative stress and inflammation, and enhances autophagy in aging rats, indicating potential benefits for age-related neurological conditions.

Combatting Obesity and Metabolic Disorders

Spermidine intake combats obesity and associated metabolic disorders by activating brown adipose tissue and adapting skeletal muscle through both hypothalamus-dependent and independent mechanisms.

Therapeutic Treatment for Genetic Translation-Related Disorders

Spermidine supplementation can partially correct protein translation issues caused by mutations in the EIF5A gene, suggesting its potential as a therapeutic treatment for genetic translation-related disorders.

Universal Anti-Aging Treatment

The external addition of spermidine can extend lifespan and reduce protein damage related to aging in various organisms, indicating its potential as a universal anti-aging treatment.

Autophagy and Longevity

Spermidine induces autophagy in yeast, mammalian cells, nematodes, and flies, which is essential for its life-extending and necrosis-suppressing effects.

Relationship Between Sirtuin-1 and Autophagy

Sirtuin-1 activation, through agents like resveratrol or genetic alterations, initiates autophagy and is necessary for autophagy in response to nutrient deprivation, but not for autophagy activated by downstream signals.

Cardioprotective Effect During Acute Myocardial Infarction

Pretreatment with spermidine reduces cardiac dysfunction during acute myocardial infarction by promoting autophagy and enhancing the heart's antioxidant capacity.

Delaying Aging in Mesenchymal Stromal Cells

Early administration of spermidine significantly delays senescence in human umbilical cord mesenchymal stem cells, maintaining their proliferation and differentiation capabilities.

Liver Endothelium Protection

Dietary spermidine supplementation during early phases of liver disease can protect the liver endothelium from oxidative stress and could alter the progression of chronic liver diseases.

Autophagy Decline and Aging

Spermidine can extend lifespan and improve cellular function by promoting autophagy, which decreases with age and leads to cellular damage accumulation.

Neurological Health and Therapeutic Potential

Spermidine's neuroprotective effects, including anti-aging, anti-inflammatory, and neurotoxicity prevention properties, could be beneficial in treating age-related neurological disorders.

Dietary Polyamines and Health

Dietary polyamines such as putrescine, spermine, and spermidine are critical for cell growth, DNA stabilization, and immune response, and may be supplemented in infant formulas to support neonatal gut development.

References:

1. Beneficial effects of spermidine on cardiovascular health and longevity suggest a cell type-specific import of polyamines by cardiomyocytes
2. Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification
3. Spermidine suppresses the activation of hepatic stellate cells to cure liver fibrosis through autophagy activator MAP1S
4. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol
5. Association of spermidine plasma levels with brain aging in a population-based study
6. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?
7. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
8. Computational biology-based study of the molecular mechanism of spermidine amelioration of acute pancreatitis
9. Polyamines and Aging: A CLEAR Connection?
10. Spermidine-triggered autophagy ameliorates memory during aging
11. Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer
12. Nutritional Aspects of Spermidine
13. Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging
14. Protective Role of Spermidine in Colitis and Colon Carcinogenesis
15. Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function
16. Nutrition and longevity - From mechanisms to uncertainties
17. Natural Activators of Autophagy Reduce Oxidative Stress and Muscle Injury Biomarkers in Endurance Athletes: A Pilot Study
18. Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study
19. The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial
20. Spermidine suppresses oxidative stress and ferroptosis by Nrf2/HO-1/GPX4 and Akt/FHC/ACSL4 pathway to alleviate ovarian damage
21. Advancements in therapeutic drugs targeting of senescence
22. Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S-Mediated Noncanonical Mechanism
23. Dietary spermidine for lowering high blood pressure
24. Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence
25. Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging
26. Spermidine improves angiogenic capacity of senescent endothelial cells, and enhances ischemia-induced neovascularization in aged mice
27. Induction of autophagy by spermidine promotes longevity
28. Molecular basis of the 'anti-aging' effect of spermidine and other natural polyamines - a mini-review
29. Cardioprotection and lifespan extension by the natural polyamine spermidine
30. Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice
31. Polyamine catabolism is enhanced after traumatic brain injury
32. Extracellular Spermine Activates DNA Methyltransferase 3A and 3B
33. Spermidine Promotes Cardioprotective Autophagy
34. Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein
35. Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury
36. The positive effect of spermidine in older adults suffering from dementia after 1 year
37. Spermidine inhibits vascular calcification in chronic kidney disease through modulation of SIRT1 signaling pathway
38. The curious case of polyamines: spermidine drives reversal of B cell senescence
39. Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge
40. Polyamines in Ovarian Aging and Disease
41. Spermidine supplementation influences mitochondrial number and morphology in the heart of aged mice
42. eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction
43. Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice
44. Dietary spermidine improves cognitive function
45. Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging
46. Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet-Induced Obesity and Metabolic Disorders
47. Spermidine supplementation in rare translation-associated disorders
48. Spermidine: a novel autophagy inducer and longevity elixir
49. The life span-prolonging effect of sirtuin-1 is mediated by autophagy
50. A study of the cardioprotective effect of spermidine: A novel inducer of autophagy
51. Spermidine Retarded the Senescence of Multipotent Mesenchymal Stromal Cells In Vitro and In Vivo through SIRT3-Mediated Antioxidation
52. Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
53. Polyamines reverse immune senescence via the translational control of autophagy
54. Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders
55. Biological significance of dietary polyamines

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