bims-polyam Biomed News
on Polyamines
Issue of 2024–09–15
six papers selected by
Sebastian J. Hofer, University of Graz
  1. A genetically encoded fluorescent reporter for polyamines.
  2. Protective effects of spermidine levels against cardiovascular risk factors: An exploration of causality based on a bi-directional Mendelian randomization analysis.
  3. Aging-Related Metabolome Analysis of the Masseter Muscle in Senescence-Accelerated Mouse-Prone 8.
  4. ODC1, a key enzyme in polyamine metabolism, plays a regulatory role in B cell differentiation.
  5. Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer.
  6. The longevity factor spermidine is part of a highly heritable complex erythrocyte phenotype associated with longevity.
  1. bioRxiv. 2024 Aug 26. pii: 2024.08.24.609500. [Epub ahead of print]
    A genetically encoded fluorescent reporter for polyamines.
    Pushkal Sharma, Colin Y Kim, Heather R Keys, Shinya Imada, Alexander B Joseph, Luke Ferro, Tenzin Kunchok, Rachel Anderson, Omer H Yilmaz, Jing-Ke Weng, Ankur Jain.
      Polyamines are abundant and evolutionarily conserved metabolites that are essential for life. Dietary polyamine supplementation extends life-span and health-span. Dysregulation of polyamine homeostasis is linked to Parkinson's disease and cancer, driving interest in therapeutically targeting this pathway. However, measuring cellular polyamine levels, which vary across cell types and states, remains challenging. We introduce a first-in-class genetically encoded polyamine reporter for real-time measurement of polyamine concentrations in single living cells. This reporter utilizes the polyamine-responsive ribosomal frameshift motif from the OAZ1 gene. We demonstrate broad applicability of this approach and reveal dynamic changes in polyamine levels in response to genetic and pharmacological perturbations. Using this reporter, we conducted a genome-wide CRISPR screen and uncovered an unexpected link between mitochondrial respiration and polyamine import, which are both risk factors for genetic Parkinson's disease. By offering a new lens to examine polyamine biology, this reporter may advance our understanding of these ubiquitous metabolites and accelerate therapy development.
    DOI:  https://doi.org/10.1101/2024.08.24.609500
  2. Nutrition. 2024 Aug 05. pii: S0899-9007(24)00198-9. [Epub ahead of print]127 112549
    Protective effects of spermidine levels against cardiovascular risk factors: An exploration of causality based on a bi-directional Mendelian randomization analysis.
    Tianyi Wang, Na Li, Yong Zeng.
      The study investigated the causal relationships between spermidine levels and CVD risk factors using a bi-directional MR approach. Employing genetic variants from extensive GWAS datasets as IVs, the study aimed to determine whether spermidine levels can influence CVD risk factors such as blood pressure, blood glucose, and lipid profiles, and vice versa. The findings suggest a protective role of elevated spermidine levels against hypertension, elevated blood glucose, and lipid profiles (LDL-C and HDL-C). Specifically, increased spermidine levels were significantly associated with lower risk of hypertension (IVW beta = -0.0013453913, p = 0.01597648) and suppression risk of elevated blood glucose (IVW beta = -0.08061330, p = 0.02450205). Additionally, there was a notable association with lipid modulation, showing a decrease in LDL-C (IVW beta = -0.01849161, p = 0.01086728) and an increase in HDL-C (IVW beta = 0.0044608332, P = 0.01760051). Conversely, the influence of CVD risk factors on spermidine levels was minimal, with the exception that elevated blood glucose levels resulted in reduced spermidine levels. (IVW beta = -0.06714391, P = 0.01096123). These results underline the potential of spermidine as a modifiable dietary target for the prevention and management of cardiovascular diseases. Further investigations are warranted to explore the underlying biological mechanisms and the applicability of these findings in broader and diverse populations.
    Keywords:  Cardiovascular disease prevention; GWAS (Genome-Wide Association Studies); Genetic epidemiology; Mendelian randomization; Spermidine
    DOI:  https://doi.org/10.1016/j.nut.2024.112549
  3. Int J Mol Sci. 2024 Sep 07. pii: 9684. [Epub ahead of print]25(17):
    Aging-Related Metabolome Analysis of the Masseter Muscle in Senescence-Accelerated Mouse-Prone 8.
    Yoshiaki Kato, Teruhide Hoshino, Yudai Ogawa, Keisuke Sugahara, Akira Katakura.
      Frailty is a vulnerable state that marks the transition to long-term care for older people. Early detection and prevention of sarcopenia, the main symptom of frailty, are important to ensure an excellent quality of life for older people. Recently, the relationship between frailty, sarcopenia, and oral function has been attracting attention. This study aimed to clarify the changes in metabolites and metabolic pathways due to aging in the masseter muscle of senescence-accelerated mouse-prone 8 (SAMP8) mice. A capillary electrophoresis-mass spectrometry metabolome analysis was performed on the masseter muscle of 12-week-old, 40-week-old, and 55-week-old mice. The expression of enzymes involved in metabolome pathways considered to be related to aging was confirmed using reverse transcription polymerase chain reaction. Clear metabolic fluctuations were observed between 12, 40-week-old, and 55-week-old SAMP8 mice. The extracted metabolic pathways were the glycolysis, polyamine metabolome, and purine metabolome pathways. Nine fluctuated metabolites were common among the groups. Spermidine and Val were increased, which was regarded as a characteristic change in the masseter muscle due to aging. In conclusion, the age-related metabolic pathways in SAMP8 mice were the glycolysis, polyamine metabolome, and purine metabolome pathways. The increased spermidine and Val levels in the masseter muscle compared with the lower limbs are characteristic changes.
    Keywords:  aging; masseter muscle; metabolites; metabolome analysis; senescence-accelerated mouse
    DOI:  https://doi.org/10.3390/ijms25179684
  4. Asian J Surg. 2024 Sep 05. pii: S1015-9584(24)01904-3. [Epub ahead of print]
    ODC1, a key enzyme in polyamine metabolism, plays a regulatory role in B cell differentiation.
    Yingzhu Xiong, Ming Lei, Yan Gao, Yi Deng.
      
    DOI:  https://doi.org/10.1016/j.asjsur.2024.08.164
  5. J Clin Med. 2024 Sep 02. pii: 5202. [Epub ahead of print]13(17):
    Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer.
    Tetsuo Ishizaki, Masahiro Sugimoto, Yu Kuboyama, Junichi Mazaki, Kenta Kasahara, Tomoya Tago, Ryutaro Udo, Kenichi Iwasaki, Yutaka Hayashi, Yuichi Nagakawa.
      Background/Objectives: The objective of this study was to investigate the metabolomic profiles of patients with colorectal cancer (CRC) across various stages of the disease. Methods: The plasma samples were obtained from 255 subjects, including patients with CRC in stages I-IV, polyps, and controls. We employed capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography triple quadrupole mass spectrometry to analyze hydrophilic metabolites comprehensively. The data were randomly divided into two groups, and consistent differences observed in both groups were analyzed. Results: Acetylated polyamines, such as N1-acetylspermine and N1, N12-diacetylspermine, consistently showed elevated concentrations in stage IV compared to stages I-III. Non-acetylated polyamines, including spermine and spermidine, exhibited increasing trends from polyp to stage IV. Other metabolites, such as histidine and o-acetylcarnitine, showed decreasing trends across stages. While acetylated polyamines have been reported as CRC detection markers, our findings suggest that they also possess diagnostic potential for distinguishing stage IV from other stages. Conclusions: This study showed stage-specific changes in metabolic profiles, including polyamines, of colorectal cancer.
    Keywords:  capillary electrophoresis–mass spectrometry; colorectal cancer; liquid chromatography–mass spectrometry; mass spectrometry; metabolomics; metastasis
    DOI:  https://doi.org/10.3390/jcm13175202
  6. Aging Cell. 2024 Sep 07. e14311
    The longevity factor spermidine is part of a highly heritable complex erythrocyte phenotype associated with longevity.
    Cameron J Kaminsky, Jericha Mill, Viharkumar Patel, Dylan Pierce, Amelia Haj, Aaron S Hess, Lingjun Li, Thomas Raife.
      Extreme longevity in humans is known to be a heritable trait. In a well-established twin erythrocyte metabolomics and proteomics database, we identified the longevity factor spermidine and a cluster of correlated molecules with high heritability estimates. Erythrocyte spermidine is 82% heritable and significantly correlated with 59 metabolites and 22 proteins. Thirty-eight metabolites and 19 proteins were >20% heritable, with a mean heritability of 61% for metabolites and 49% for proteins. Correlated metabolites are concentrated in energy metabolism, redox homeostasis, and autophagy pathways. Erythrocyte mean cell volume (MCV), an established heritable trait, was consistently negatively correlated with the top 25 biomolecules most strongly correlated with spermidine, indicating that smaller MCVs are associated with higher concentrations of spermidine and correlated molecules. Previous studies have linked larger MCVs with poorer memory, cognition, and all-cause mortality. Analysis of 432,682 unique patient records showed a linear increase in MCV with age but a significant deviation toward smaller than expected MCVs above age 86, suggesting that smaller MCVs are associated with extreme longevity. Consistent with previous reports, a subset of 78,158 unique patient records showed a significant skewing toward larger MCV values in a deceased cohort compared to an age-matched living cohort. Our study supports the existence of a complex, heritable phenotype in erythrocytes associated with health and longevity.
    Keywords:  association; erythrocytes; longevity; phenotype; spermidine
    DOI:  https://doi.org/10.1111/acel.14311
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