The positive effect of spermidine in older adults suffering from dementia

Pekar, Thomas; Bruckner, Katharina; Pauschenwein-Frantsich, Susanne; Gschaider, Anna; Oppliger, Martina; Willesberger, Julia; Ungersbäck, Petra; Wendzel, Aribert; Kremer, Alexandra; Flak, Walter; Wantke, F.; Jarisch, Reinhart

doi:10.1007/s00508-020-01758-y

Cited by 39 publications

(35 citation statements)

References 17 publications

(18 reference statements)

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“…Subsequently, ALDH3 synthetases synthesize β -alanine with β -aminopropion aldehyde. Previous studies confirmed that spermidine could trigger the autophagy process [ 23 , 24 ]. Considering the close association between spermidine and autophagy, we further investigated whether changes in spermidine affect autophagy.…”

Section: Resultsmentioning

confidence: 72%

“…In this current study, spermidine, as a major metabolite involved in β -alanine metabolism and arginine and proline metabolism pathways, was observed to be significantly increased in noise-exposed mice. Previous studies confirmed that spermidine could trigger autophagy [ 23 , 24 ]. Nowadays, increasing evidence indicates that autophagy is implicated in a great number of crucial physiological processes and involved in extensive diseases, including inflammation, cancer, neurodegenerative diseases, and cardiovascular diseases [ 34 ].…”

Section: Discussionmentioning

confidence: 71%

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Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss

Miao

Zhang

Yin

et al. 2022

BioMed Research International

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Noise-induced hearing loss (NIHL) has always been an important occupational hazard, but the exact etiopathogenesis underlying NIHL remains unclear. Herein, we aimed to find metabolic biomarkers involved in the development of NIHL based on a mouse model using a gas chromatography coupled with mass spectrometry (GC-MS) metabolomics technique. We showed that the auditory brainstem response (ABR) thresholds at the frequencies of 4, 8, 12, 16, 24, and 32 kHz were all significantly elevated in the noise-exposed mice. Noise could cause outer hair cell (OHC) loss in the base of the cochlea. A total of 17 differential metabolites and 9 metabolic pathways were significantly affected following noise exposure. Spermidine acting as an autophagy modulator was found to be 2.85-fold higher in the noise-exposed group than in the control group and involved in β-alanine metabolism and arginine and proline metabolism pathways. Additionally, we demonstrated that LC3B and Beclin1 were expressed in the spiral ganglion neurons (SGNs), and their mRNA levels were increased after noise. We showed that SOD activity was significantly decreased in the cochlea of noise-exposed mice. Further experiments suggested that SOD1 and SOD2 proteins in the SGNs were all decreased following noise exposure. The upregulation of spermidine may induce LC3B- and Beclin1-mediated autophagy in the cochlear hair cells (HCs) through β-alanine metabolism and arginine and proline metabolism and be involved in the NIHL. ROS-mediated oxidative damage may be a pivotal molecular mechanism of NIHL. Taken together, spermidine can be regarded as an important metabolic marker for the diagnosis of NIHL.

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Section: Resultsmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 71%

Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss

Miao

Zhang

Yin

et al. 2022

BioMed Research International

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“…This anti-aging effect may be associated with its ability for restoring cellular metabolic dysfunction. A study of 85 elder adults reveals that spermidine significantly improved cognitive performance ( 150 , 151 ).…”

Section: The Epigenetic Intervention Strategies Of Vascular Agingmentioning

confidence: 99%

Targeting Epigenetic Mechanisms in Vascular Aging

Lin

Ding

et al. 2022

Front. Cardiovasc. Med.

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Environment, diseases, lack of exercise, and aged tendency of population have becoming crucial factors that induce vascular aging. Vascular aging is unmodifiable risk factor for diseases like diabetes, hypertension, atherosclerosis, and hyperlipidemia. Effective interventions to combat this vascular function decline is becoming increasingly urgent as the rising hospitalization rate caused by vascular aging-related diseases. Fortunately, recent transformative omics approaches have enabled us to examine vascular aging mechanisms at unprecedented levels and precision, which make our understanding of slowing down or reversing vascular aging become possible. Epigenetic viz. DNA methylation, histone modifications, and non-coding RNA-based mechanisms, is a hallmark of vascular aging, its deregulation leads to aberrant transcription changes in tissues. Epigenetics mechanisms by mediating covalent modifications to DNA and histone proteins, consequently, influence the sensitivity and activities of signaling pathways in cells and tissues. A growing body of evidence supports correlations between epigenetic changes and vascular aging. In this article, we will provide a comprehensive overview of epigenetic changes associated with vascular aging based on the recent findings with a focus on molecular mechanisms of action, strategies to reverse epigenetic changes, and future perspectives.

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“…The same extract was previously found to be safe in mice and older humans, while not provoking changes in vital signs in the latter after 3 months ( 201 ). Another study supplemented spermidine via wheat-germ containing bread rolls (3.3 mg spermidine/piece, ~23 pieces/month) for 3 months to older adults living in nursing homes and found subtle improvements in cognitive function of patients with mild dementia ( 202 ).…”

Section: Polyaminesmentioning

confidence: 99%

Caloric Restriction Mimetics in Nutrition and Clinical Trials

et al. 2021

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The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.

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The positive effect of spermidine in older adults suffering from dementia

Cited by 39 publications

References 17 publications

Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss

Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss

Targeting Epigenetic Mechanisms in Vascular Aging

Caloric Restriction Mimetics in Nutrition and Clinical Trials

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