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      Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care—clinically relevant 3PM innovation

      research-article
      1 , , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ,
      The EPMA Journal
      Springer International Publishing
      Predictive preventive personalized medicine (PPPM / 3PM), Mitochondrial health, Mitophagy, Phytomedicine, Nutrients, Health protection, Biological age, Primary and Secondary care, Life quality, Longevity, Mitochondria-targeted substances, Sirtuins, Catechins, Vitamin B, Carnitine, L-Carnosine, Creatine, CoQ10, Resveratrol, Quercetin, Octacosanol, Pterostilbene, Alpha-lipoic acid, Senotherapeutics, Senolytics, Senomorphics, Fisetin, Piperlongumine, Curcumin, Kaempferol, Apigenin, Vitamin D, Silibinin, Allicin, Oleanolic acid, Ginseng, Melatonin, DMG-gold, Trehalose, Ginkgo biloba, Green tea, Aloe vera, Saffron, PQQ

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          Abstract

          Despite their subordination in humans, to a great extent, mitochondria maintain their independent status but tightly cooperate with the “host” on protecting the joint life quality and minimizing health risks. Under oxidative stress conditions, healthy mitochondria promptly increase mitophagy level to remove damaged “fellows” rejuvenating the mitochondrial population and sending fragments of mtDNA as SOS signals to all systems in the human body. As long as metabolic pathways are under systemic control and well-concerted together, adaptive mechanisms become triggered increasing systemic protection, activating antioxidant defense and repair machinery. Contextually, all attributes of mitochondrial patho-/physiology are instrumental for predictive medical approach and cost-effective treatments tailored to individualized patient profiles in primary (to protect vulnerable individuals again the health-to-disease transition) and secondary (to protect affected individuals again disease progression) care. Nutraceuticals are naturally occurring bioactive compounds demonstrating health-promoting, illness-preventing, and other health-related benefits. Keeping in mind health-promoting properties of nutraceuticals along with their great therapeutic potential and safety profile, there is a permanently growing demand on the application of mitochondria-relevant nutraceuticals. Application of nutraceuticals is beneficial only if meeting needs at individual level. Therefore, health risk assessment and creation of individualized patient profiles are of pivotal importance followed by adapted nutraceutical sets meeting individual needs. Based on the scientific evidence available for mitochondria-relevant nutraceuticals, this article presents examples of frequent medical conditions, which require protective measures targeted on mitochondria as a holistic approach following advanced concepts of predictive, preventive, and personalized medicine (PPPM/3PM) in primary and secondary care.

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          The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs

          The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1 −/Δ mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1 −/Δ mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.
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            Mammalian sirtuins: biological insights and disease relevance.

            Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.
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              Plant polyphenols as dietary antioxidants in human health and disease

              Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.
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                Author and article information

                Contributors
                Olga.Golubnitschaja@ukbonn.de
                peter.kubatka@uniba.sk
                Journal
                EPMA J
                EPMA J
                The EPMA Journal
                Springer International Publishing (Cham )
                1878-5077
                1878-5085
                18 April 2024
                18 April 2024
                June 2024
                : 15
                : 2
                : 163-205
                Affiliations
                [1 ]GRID grid.10388.32, ISNI 0000 0001 2240 3300, Predictive, Preventive and Personalised (3P) Medicine, Department of Radiation Oncology, , University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, ; 53127 Bonn, Germany
                [2 ]Biomedical Centre Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, ( https://ror.org/0587ef340) 036 01 Martin, Slovakia
                [3 ]Max Planck Institute for Plant Breeding Research, ( https://ror.org/044g3zk14) Carl-Von-Linne-Weg 10, 50829 Cologne, Germany
                [4 ]GRID grid.11175.33, ISNI 0000 0004 0576 0391, Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, , P. J. Šafárik University in Košice, ; 040 01 Košice, Slovakia
                [5 ]Negentropic Systems, Ružomberok, Slovakia
                [6 ]PPPM Centre, s.r.o., Ruzomberok, Slovakia
                [7 ]Institute of General Medicine, University of Leipzig, ( https://ror.org/03s7gtk40) Leipzig, Germany
                [8 ]GRID grid.15090.3d, ISNI 0000 0000 8786 803X, Department of Radiation Oncology, , University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, ; 53127 Bonn, Germany
                [9 ]Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, ( https://ror.org/0587ef340) Martin, Slovakia
                Article
                358
                10.1007/s13167-024-00358-4
                11148002
                38841620
                73d28196-36ae-4de8-a519-a0cfd6b03f5d
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 March 2024
                : 25 March 2024
                Funding
                Funded by: Universitätsklinikum Bonn (8930)
                Categories
                Research
                Custom metadata
                © European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2024

                Molecular medicine
                predictive preventive personalized medicine (pppm / 3pm),mitochondrial health,mitophagy,phytomedicine,nutrients,health protection,biological age,primary and secondary care,life quality,longevity,mitochondria-targeted substances,sirtuins,catechins,vitamin b,carnitine,l-carnosine,creatine,coq10,resveratrol,quercetin,octacosanol,pterostilbene,alpha-lipoic acid,senotherapeutics,senolytics,senomorphics,fisetin,piperlongumine,curcumin,kaempferol,apigenin,vitamin d,silibinin,allicin,oleanolic acid,ginseng,melatonin,dmg-gold,trehalose,ginkgo biloba,green tea,aloe vera,saffron,pqq

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