Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 63
Filter
1.
Small Methods ; : e2301573, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546017

ABSTRACT

Thin film photovoltaic (TFPV) materials and devices present a high complexity with multiscale, multilayer, and multielement structures and with complex fabrication procedures. To deal with this complexity, the evaluation of their physicochemical properties is critical for generating a model that proposes strategies for their development and optimization. However, this process is time-consuming and requires high expertise. In this context, the adoption of combinatorial analysis (CA) and artificial intelligence (AI) strategies represents a powerful asset for accelerating the development of these complex materials and devices. This work introduces a methodology to facilitate the adoption of AI and CA for the development of TFPV technologies. The methodology covers all the necessary steps from the synthesis of samples for CA to data acquisition, AI-assisted data analysis, and the extraction of relevant information for research acceleration. Each step provides details on the necessary concepts, requirements, and procedures and are illustrated with examples from the literature. Then, the application of the methodology to a complex set of samples from a TFPV production line highlights its ability to rapidly glean significant insights even in intricate scenarios. The proposed methodology can be applied to other types of materials and devices beyond PV and using different characterization techniques.

2.
Methods Cell Biol ; 181: 87-108, 2024.
Article in English | MEDLINE | ID: mdl-38302246

ABSTRACT

Chronological age represents the time that passes between birth and a given date. To understand the complex network of factors contributing to chronological lifespan, a variety of model organisms have been implemented. One of the best studied organisms is the yeast Saccharomyces cerevisiae, which has greatly contributed toward identifying conserved biological mechanisms that act on longevity. Here, we discuss high- und low-throughput protocols to monitor and characterize chronological lifespan and chronological aging-associated cell death in S. cerevisiae. Included are propidium iodide staining with the possibility to quantitatively assess aging-associated cell death via flow cytometry or qualitative assessments via microscopy, cell viability assessment through plating and cell counting and cell death characterization via propidium iodide/AnnexinV staining and subsequent flow cytometric analysis or microscopy. Importantly, all of these methods combined give a clear picture of the chronological lifespan under different conditions or genetic backgrounds and represent a starting point for pharmacological or genetic interventions.


Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Propidium/metabolism , Saccharomyces cerevisiae Proteins/metabolism
3.
Animals (Basel) ; 14(3)2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38338022

ABSTRACT

From a cost and sustainability perspective, the use of by-products such as rye bran in sow diets is of particular interest. Rye bran has valuable ingredients that have potential benefits for the gut health of sows. The aim of this study was to investigate the effects of including 15% rye bran in the sows' feed on the performance of sows and piglets. The feeding started one week before the farrowing date and ended at weaning. Performance was evaluated by measuring sow (n = 175) and piglet body weight (n = 1372) and sows' backfat thickness (n = 80). These data were additionally used to calculate the colostrum intake of the suckling piglets and the sows' milk production. It was found that there were no differences in the performance parameters between the experimental and control groups. However, this study showed that the piglets with light birth weight (LBW (<1000 g)) and medium birth weight (MBW (1000-1500 g) consumed more colostrum when the sows were fed rye bran (LBW: C/R 203.0 ± 39.2 g/214.3 ± 35.9 g; MBW: 291.3 ± 39.0 g/298.5 ± 36.4 g). It can be concluded that including 15% rye bran in the feed of lactating sows has no obvious negative effects on the performance of sows and piglets. Further studies are needed to evaluate the possible positive effects of rye bran.

4.
Eur J Clin Invest ; 54(4): e14138, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38041247

ABSTRACT

Mitochondrial dysfunction is a major hallmark of ageing and related chronic disorders. Controlled removal of damaged mitochondria by the autophagic machinery, a process known as mitophagy, is vital for mitochondrial homeostasis and cell survival. The central role of mitochondria in cellular metabolism places mitochondrial removal at the interface of key metabolic pathways affecting the biosynthesis or catabolism of acetyl-coenzyme A, nicotinamide adenine dinucleotide, polyamines, as well as fatty acids and amino acids. Molecular switches that integrate the metabolic status of the cell, like AMP-dependent protein kinase, protein kinase A, mechanistic target of rapamycin and sirtuins, have also emerged as important regulators of mitophagy. In this review, we discuss how metabolic regulation intersects with mitophagy. We place special emphasis on the metabolic regulatory circuits that may be therapeutically targeted to delay ageing and mitochondria-associated chronic diseases. Moreover, we identify outstanding knowledge gaps, such as the ill-defined distinction between basal and damage-induced mitophagy, which must be resolved to boost progress in this area.


Subject(s)
Mitochondria , Mitophagy , Humans , Mitophagy/physiology , Mitochondria/physiology , Autophagy , Homeostasis
6.
Animals (Basel) ; 13(14)2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37508038

ABSTRACT

The nutritional benefits of rye (and therefore rye bran) are mainly due to its high content of fermentable dietary fiber, the non-starch polysaccharides (NSP). Microorganisms in the large intestine are able to convert these into short-chain fatty acids (SCFA), including butyrate. Butyrate strengthens the epithelial barrier function in the colon by nourishing the enterocytes and inhibiting the spread of Salmonella in the intestinal tract. Therefore, the aim of this study was to test under field conditions whether a diet with rye or rye bran as the main ingredient for gilts, sows, and weaned piglets is associated with a lower Salmonella prevalence. Depending on the age groups, between 20-30% rye or between 15-20% rye bran was used in the experimental group. A total of n = 1983 boot swabs, n = 356 fecal samples, and n = 1909 serum samples were examined. The results of this study show that rye or rye bran at the levels used had no apparent effect on the number of positive Salmonella samples. However, the Salmonella OD values in the experimental groups were significantly lower than in the control group. This suggests that the use of rye leads to a lower incidence of infection, but this effect could not be proven from swabs.

7.
Cell Stress ; 7(7): 50-58, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37431488

ABSTRACT

Spermidine is a ubiquitous, natural polyamine with geroprotective features. Supplementation of spermidine extends the lifespan of yeast, worms, flies, and mice, and dietary spermidine intake correlates with reduced human mortality. However, the crucial role of polyamines in cell proliferation has also implicated polyamine metabolism in neoplastic diseases, such as cancer. While depleting intracellular polyamine biosynthesis halts tumor growth in mouse models, lifelong external spermidine administration in mice does not increase cancer incidence. In contrast, a series of recent findings points to anti-neoplastic properties of spermidine administration in the context of immunotherapy. Various molecular mechanisms for the anti-aging and anti-cancer properties have been proposed, including the promotion of autophagy, enhanced translational control, and augmented mitochondrial function. For instance, spermidine allosterically activates mitochondrial trifunctional protein (MTP), a bipartite protein complex that mediates three of the four steps of mitochondrial fatty acid (ß-oxidation. Through this action, spermidine supplementation is able to restore MTP-mediated mitochondrial respiratory capacity in naïve CD8+ T cells to juvenile levels and thereby improves T cell activation in aged mice. Here, we put this finding into the context of the previously described molecular target space of spermidine.

8.
Cardiology ; 148(5): 402-408, 2023.
Article in English | MEDLINE | ID: mdl-37369183

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) adversely impacts right ventricular (RV) and right atrial (RA) structure and function. There are limited data on these changes after electrical cardioversion (ECV) and the relative contribution of heart rate to evaluate the immediate (1-2 h) and short-term (4-6 weeks) changes in right cardiac chamber dimensions and RV function after ECV in patients with persistent AF. METHODS: Right cardiac chamber dimensions and RV function were measured in 64 patients using transthoracic echocardiography 1-2 h before, immediately after, and 4-6 weeks after ECV. Associations between changes in right-heart measures and rhythm status at follow-up were assessed using linear regression models. RESULTS: For patients who remained in sinus rhythm 4-6 weeks after ECV (n = 48), median fractional area change (FAC) at baseline, immediately after ECV, and 4-6 weeks after ECV were 39 (Q1:35, Q3:42) %, 42 (Q1:39, Q3:46) %, 46 (Q1:43, Q3:49) % (p < 0.01); median tricuspid annular plane systolic excursion (TAPSE) values at the same time points were 18 (Q1:17, Q3:20) mm, 20 (Q1:18, Q3:23) mm, and 24 (Q1:22, Q3:26) mm (p < 0.01), respectively. There was no significant difference in RV end systolic area and RA volume index before and after ECV. However, RV end systolic area and RA volume index decreased significantly after 4-6 weeks from a median of 10 (Q1:8, Q3:13) cm2 to 8 (Q1:7, Q3:10) cm2 (p < 0.01), and from a median of 30 (Q1:24, Q3:36) mL/m2 to 24 (Q1:20, Q3:27) mL/m2 (p < 0.01). Changes in TAPSE were significantly associated with sinus rhythm at follow-up (p = 0.027), changes in FAC showed a strong trend to association with sinus rhythm (p = 0.053), and this was not true for RA measures (p = 0.64). CONCLUSIONS: Among AF patients who remained in sinus rhythm after ECV, RV function improved immediately after ECV with further improvement at 4-6 weeks following sinus rhythm restoration.


Subject(s)
Atrial Fibrillation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/therapy , Electric Countershock , Heart Atria/diagnostic imaging , Heart Rate/physiology , Echocardiography , Ventricular Function, Right
9.
Bioresour Bioprocess ; 10(1): 59, 2023 Sep 02.
Article in English | MEDLINE | ID: mdl-38647610

ABSTRACT

AIM: Stillage, the main residue from cereal-based bioethanol production, offers a great potential for the recovery of pentosan-type carbohydrates. Therefore, potential process options for the recovery of pentosans from bioethanol thin stillage are investigated and their basic feasibility is demonstrated on a laboratory scale. FINDINGS: The main result of this work is the development of a three-stage process for pentosan recovery, including solid-liquid separation, pentosan solubilisation and purification. The pentosan content of the thin stillage used here was determined to be about 14% related to dry matter (DM). By means of solid-liquid separation, these pentosans accumulate in the liquid phase (up to 80%), while the remainder (about 20%) is found in the solid phase. Solubilisation of these insoluble pentosans was achieved by using either a hydrothermal, an alkaline or an enzymatic treatment. Here, the results indicate a maximum solubilisation yield of 90% with a hydrothermal treatment using liquid hot water at 180 °C. Ultrafiltration and precipitation are investigated for purification. The most promising process option in this study is solid-liquid separation followed by ultrafiltration. In this case, the total pentosan yield is assessed to be about 48% (based on thin stillage) with a final pentosan concentration of about 30%DM.

10.
Front Cardiovasc Med ; 9: 869501, 2022.
Article in English | MEDLINE | ID: mdl-35783836

ABSTRACT

Aim: Due to insufficient evidence on the safety and effectiveness of high-intensity interval training (HIIT) in patients early after ST-segment elevation myocardial infarction (STEMI), we aimed to compare short- and long-term effects of randomized HIIT or moderate-intensity continuous training (MICT) on markers of left ventricular (LV) remodeling in STEMI patients receiving optimal guideline-directed medical therapy (GDMT). Materials and Methods: Patients after STEMI (<4 weeks) enrolled in a 12-week cardiac rehabilitation (CR) program were recruited for this randomized controlled trial (NCT02627586). During a 3-week run-in period with three weekly MICT sessions, GDMT was up-titrated. Then, the patients were randomized to HIIT or isocaloric MICT for 9 weeks. Echocardiography and cardiopulmonary exercise tests were performed after run-in (3 weeks), end of CR (12 weeks), and at 1-year follow-up. The primary outcome was LV end-diastolic volume index (LVEDVi) at the end of CR. Secondary outcomes were LV global longitudinal strain (GLS) and cardiopulmonary fitness. Results: Seventy-three male patients were included, with the time between STEMI and start of CR and randomization being 12.5 ± 6.3 and 45.8 ± 10.8 days, respectively. Mixed models revealed no significant group × time interaction for LVEDVi at the end of CR (p = 0.557). However, there was a significantly smaller improvement in GLS at 1-year follow-up in the HIIT compared to the MICT group (p = 0.031 for group × time interaction). Cardiorespiratory fitness improved significantly from a median value of 26.5 (1st quartile 24.4; 3rd quartile 1.1) ml/kg/min at randomization in the HIIT and 27.7 (23.9; 31.6) ml/kg/min in the MICT group to 29.6 (25.3; 32.2) and 29.9 (26.1; 34.9) ml/kg/min at the end of CR and to 29.0 (26.6; 33.3) and 30.6 (26.0; 33.8) ml/kg/min at 1 year follow-up in HIIT and MICT patients, respectively, with no significant group × time interactions (p = 0.138 and 0.317). Conclusion: In optimally treated patients early after STEMI, HIIT was not different from isocaloric MICT with regard to short-term effects on LVEDVi and cardiorespiratory fitness. The worsening in GLS at 1 year in the HIIT group deserves further investigation, as early HIIT may offset the beneficial effects of GDMT on LV remodeling in the long term.

11.
Microb Cell ; 9(4): 72-79, 2022 Apr 04.
Article in English | MEDLINE | ID: mdl-35434121

ABSTRACT

Viral, bacterial, fungal and protozoal biology is of cardinal importance for the evolutionary history of life, ecology, biotechnology and infectious diseases. Various microbiological model systems have fundamentally contributed to the understanding of molecular and cellular processes, including the cell cycle, cell death, mitochondrial biogenesis, vesicular fusion and autophagy, among many others. Microbial interactions within the environment have profound effects on many fields of biology, from ecological diversity to the highly complex and multifaceted impact of the microbiome on human health. Also, biotechnological innovation and corresponding industrial operations strongly depend on microbial engineering. With this wide range of impact in mind, the peer-reviewed and open access journal Microbial Cell was founded in 2014 and celebrates its 100th issue this month. Here, we briefly summarize how the vast diversity of microbiological subjects influences our personal and societal lives and shortly review the milestones achieved by Microbial Cell during the last years.

12.
EMBO Mol Med ; 14(5): e13952, 2022 05 09.
Article in English | MEDLINE | ID: mdl-35373908

ABSTRACT

Amyloid beta 42 (Abeta42) is the principal trigger of neurodegeneration during Alzheimer's disease (AD). However, the etiology of its noxious cellular effects remains elusive. In a combinatory genetic and proteomic approach using a yeast model to study aspects of intracellular Abeta42 toxicity, we here identify the HSP40 family member Ydj1, the yeast orthologue of human DnaJA1, as a crucial factor in Abeta42-mediated cell death. We demonstrate that Ydj1/DnaJA1 physically interacts with Abeta42 (in yeast and mouse), stabilizes Abeta42 oligomers, and mediates their translocation to mitochondria. Consequently, deletion of YDJ1 strongly reduces co-purification of Abeta42 with mitochondria and prevents Abeta42-induced mitochondria-dependent cell death. Consistently, purified DnaJ chaperone delays Abeta42 fibrillization in vitro, and heterologous expression of human DnaJA1 induces formation of Abeta42 oligomers and their deleterious translocation to mitochondria in vivo. Finally, downregulation of the Ydj1 fly homologue, Droj2, improves stress resistance, mitochondrial morphology, and memory performance in a Drosophila melanogaster AD model. These data reveal an unexpected and detrimental role for specific HSP40s in promoting hallmarks of Abeta42 toxicity.


Subject(s)
Alzheimer Disease , Saccharomyces cerevisiae Proteins , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Drosophila melanogaster/metabolism , HSP40 Heat-Shock Proteins/genetics , Mice , Molecular Chaperones , Peptide Fragments/metabolism , Peptide Fragments/toxicity , Proteomics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism
13.
Infection ; 50(4): 925-932, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35182355

ABSTRACT

PURPOSE: Evidence on the effect of self-protection via social distancing and wearing face-masks on infections during chemotherapy is currently not available. We asked if the occurrence of acute infections during chemotherapy for advanced-stage Hodgkin lymphoma (HL) decreased when COVID-19 protection measures were in effect. METHODS: We analyzed the occurrence of infections during all documented eBEACOPP cycles starting between 01 March and 30 June of 2017 to 2020 in patients treated within the GHSG HD21 study in Germany and compared the infection rates and characteristics by logistic regression models and means of descriptive statistics. RESULTS: We analyzed 911 cycles of 313 adult patients treated with 4 to 6 cycles of eBEACOPP. We found a significant decrease in the occurrence of infections during chemotherapy for HL during COVID-19 lockdown from 131 (19.6%) of 670 cycles in 2017-2019 to 30 (12.6%) of 239 cycles during COVID-19 lockdown [OR 0.574 (95% CI 0.354-0.930), P = 0.024]. The strongest effect was evident for unspecified infections with 39 cycles (5.8%) during 2017-2019 in comparison to 5 cycles (2.1%) during COVID-19 lockdown. 20 (24.1%) of 83 patients had an infection during the COVID-19 lockdown versus 99 (43.2%) of 229 patients in the years 2017-2019 (P = 0.0023). CONCLUSION: The significant decrease of infections during chemotherapy for HL during COVID-19 lockdown reveals the protective measures' potential to shield patients from transmissible pathogens. We conclude that these measures could be recommended for HL patients at risk for infections during chemotherapy.


Subject(s)
COVID-19 , Hodgkin Disease , Infections , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/adverse effects , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Doxorubicin/adverse effects , Hodgkin Disease/drug therapy , Hodgkin Disease/epidemiology , Humans , Infections/drug therapy
15.
Dtsch Med Wochenschr ; 146(20): 1360-1368, 2021 10.
Article in German | MEDLINE | ID: mdl-34644797

ABSTRACT

The main symptom of hemorrhagic diathesis is an increased bleeding tendency. Due to the subjectivity of various features of the bleeding history, unclarity of the family history, and an individualization of the extent of diagnostic the evaluation of a suspected bleeding disorder represents a challenging endeavour in hematology. Hemorrhagic diathesis can be divided into the following sub-categories: disorders in primary hemostasis (e. g. von Willebrand disease, different causes of thrombocytopenia), secondary hemostasis (e. g. hemophilia A and B, Vitamin K deficiency) and fibrinolysis, and in connective tissue or vascular formation. This article reviews available diagnostic methods for bleeding disorders, from structured patient history to highly specialized laboratory diagnosis.


Subject(s)
Clinical Laboratory Techniques , Hemorrhage/diagnosis , Medical History Taking , Physical Examination , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standards , Diagnosis, Differential , Hemorrhage/classification , Hemorrhage/physiopathology , Humans , Medical History Taking/methods , Medical History Taking/standards , Partial Thromboplastin Time , Physical Examination/methods , Physical Examination/standards , Platelet Function Tests , Thrombocytopenia/classification , Thrombocytopenia/diagnosis , Thrombocytopenia/physiopathology
16.
Oncol Res Treat ; 44(11): 637-640, 2021.
Article in English | MEDLINE | ID: mdl-34547751

ABSTRACT

INTRODUCTION: Infectious complications represent a major cause of morbidity and mortality in hairy cell leukemia (HCL) patients. Due to the immunosuppressive nature of the disease, these patients are frequently affected by opportunistic infections and rare pathogens. Furthermore, cytotoxic chemotherapy might lead to poor or even fatal outcomes in the setting of an active infection. CASE PRESENTATION: We report the case of a 62-year-old HCL patient who presented with recurrent fever episodes, pancytopenia, and mediastinal lymphadenopathy. A treatment decision against purine analogs and for rituximab mono was made as lymph node tissue revealed disseminated Mycobacterium kansasii infection. Together with specific antimycobacterial treatment, rituximab mono led to complete hematologic remission after 6 months without aggravating the accompanying infection. CONCLUSION: Here, we demonstrate successful treatment of HCL with rituximab in a patient with concomitant disseminated M. kansasii infection.


Subject(s)
Leukemia, Hairy Cell , Mycobacterium Infections, Nontuberculous , Opportunistic Infections , Rituximab/therapeutic use , Humans , Leukemia, Hairy Cell/complications , Leukemia, Hairy Cell/drug therapy , Middle Aged , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium kansasii , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy
17.
Autophagy ; 17(8): 2037-2039, 2021 08.
Article in English | MEDLINE | ID: mdl-34105442

ABSTRACT

Spermidine is a natural polyamine, central to cellular homeostasis and growth, that promotes macroautophagy/autophagy. The polyamine pathway is highly conserved from bacteria to mammals and spermidine (prominently found in some kinds of aged cheese, wheat germs, nuts, soybeans, and fermented products thereof, among others) is an intrinsic part of the human diet. Apart from nutrition, spermidine is available to mammalian organisms from intracellular biosynthesis and microbial production in the gut. Importantly, externally supplied spermidine (via drinking water or food) prolongs lifespan, activates autophagy, improves mitochondrial function, and refills polyamine pools that decline during aging in various tissues of model organisms, including mice. In two adjacent studies, we explored how dietary spermidine supplementation enhances eEF5/EIF5A hypusination, cerebral mitochondrial function and cognition in aging Drosophila melanogaster and mice.


Subject(s)
Aging/physiology , Autophagy/drug effects , Cognition/drug effects , Mitochondria/drug effects , Spermidine/pharmacology , Animals , Humans , Longevity/drug effects , Mitochondria/metabolism
18.
Cell Rep ; 35(2): 108985, 2021 04 13.
Article in English | MEDLINE | ID: mdl-33852843

ABSTRACT

Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.


Subject(s)
Aging/genetics , Autophagy-Related Protein 7/genetics , Cognitive Dysfunction/genetics , Dietary Supplements , Protein Kinases/genetics , Spermidine/pharmacology , Ubiquitin-Protein Ligases/genetics , Aging/metabolism , Animals , Autophagy-Related Protein 7/metabolism , Brain/cytology , Brain/drug effects , Brain/growth & development , Brain/metabolism , Cognition/drug effects , Cognition/physiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/prevention & control , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Female , Gene Expression Regulation , Humans , Learning/drug effects , Learning/physiology , Male , Mice , Mitochondria/drug effects , Mitochondria/genetics , Mitochondria/metabolism , Neurons/drug effects , Neurons/metabolism , Oxidative Phosphorylation/drug effects , Protein Kinases/metabolism , Signal Transduction , Spatial Memory/drug effects , Spatial Memory/physiology , Ubiquitin-Protein Ligases/metabolism
19.
Front Cell Dev Biol ; 9: 656201, 2021.
Article in English | MEDLINE | ID: mdl-33777963

ABSTRACT

Human life expectancy continues to grow globally, and so does the prevalence of age-related chronic diseases, causing a huge medical and economic burden on society. Effective therapeutic options for these disorders are scarce, and even if available, are typically limited to a single comorbidity in a multifaceted dysfunction that inevitably affects all organ systems. Thus, novel therapies that target fundamental processes of aging itself are desperately needed. In this article, we summarize current strategies that successfully delay aging and related diseases by targeting mitochondria and protein homeostasis. In particular, we focus on autophagy, as a fundamental proteostatic process that is intimately linked to mitochondrial quality control. We present genetic and pharmacological interventions that effectively extend health- and life-span by acting on specific mitochondrial and pro-autophagic molecular targets. In the end, we delve into the crosstalk between autophagy and mitochondria, in what we refer to as the mitochondria-proteostasis axis, and explore the prospect of targeting this crosstalk to harness maximal therapeutic potential of anti-aging interventions.

20.
Cell Stress ; 5(3): 29-32, 2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33688620

ABSTRACT

The polyamine spermidine is essential for protein translation in eukaryotes, both as a substrate for the hypusination of the translation initiation factor eIF5A as well as general translational fidelity. Dwindling spermidine levels during aging have been implicated in reduced immune cell function through insufficient eIF5A hypusination, which can be restored by external supplementation. Recent findings characterize a group of novel Mendelian disorders linked to EIF5A missense and nonsense variants that cause protein translation defects. In model organisms that recapitulate these mutations, spermidine supplementation was able to alleviate at least some of the concomitant protein translation defects. Here, we discuss the role of spermidine in protein translation and possible therapeutic avenues for translation-associated disorders.

SELECTION OF CITATIONS
SEARCH DETAIL
...