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Biotechnologically produced moss active improves skin resilience
Abstract
Mosses substantially helped changing primitive earth into a green planet before vascular plants even existed. They encode genes and proteins for extraordinary resilience long abandoned by higher plants. Biotechnology offers a sterile production of the moss Physcomitrella patens in a reproducible and sustainable way. MossCellTec™ No. 1 is the first biotechnological mossbased product for cosmetic application. In our research, we have investigated the importance of cell nucleus health as a novel target for anti-aging cosmetics. Interestingly, the moss extract was able to improve the expression of cell nucleus health markers in aged skin cells. Additionally, the active ingredient could improve the hot-humid/cold-dry adaptation of reconstructed skin and improved skin homogeneity, barrier and hydration despite stressful weather conditions in a placebo-controlled clinical study. The moss active may therefore enhance the general resilience of the skin against environmental changes.
... In our in-silico experiments targeted Estradiol 17β-dehydrogenase 1 (17β-HSD1), it appears that ceruchinol, mostly present as a major component of the CO 2 extract, has the potential to inhibit the catalyzed conversion of estrogen E1 to the more active E2 ( Figure 18). This inhibitory effect is noteworthy, as it suggests a mechanism for controlling local E2 levels by targeting 17β-HSD1 [49,50]. However, our coupling study could not deliver a proper effect on that interaction. ...
... In our in-silico experiments targeted Estradiol 17β-dehydrogenase 1 (17β-HSD1), it appears that ceruchinol, mostly present as a major component of the CO2 extract, has the potential to inhibit the catalyzed conversion of estrogen E1 to the more active E2 (Figure 18). This inhibitory effect is noteworthy, as it suggests a mechanism for controlling local E2 levels by targeting 17β-HSD1 [49,50]. However, our coupling study could not deliver a proper effect on that interaction. ...
The moss Physcomitrium patens (P. patens), formerly known as Physcomitrella patens, has ascended to prominence as a pivotal model organism in plant biology. Its simplicity in structure and life cycle, coupled with genetic amenability, has rendered it indispensable in unraveling the complexities of land plant evolution and responses to environmental stimuli. As an evolutionary bridge between algae and vascular plants, P. patens offers a unique perspective on early terrestrial adaptation. This research involved the biotechnological cultivation of P. patens, followed by a deep phytochemical investigation of two extracts covering a large polarity range together using an NMR-based dereplication approach combined with GC/MS analyses. Subsequently, a multidisciplinary approach combining bioinformatics, in-silico techniques, and traditional methods was adopted to uncover intriguing molecules such as the diterpene ceruchinol and its potential receptor interactions for future cosmetic applications. The kaurene diterpene ceruchinol, representing up to 50% of the supercritical CO2 extract and also identified in the hydroalcoholic extract, was selected for the molecular docking study, which highlighted several biological targets as CAR, AKR1D1, and 17β-HSD1 for potential cosmetic use. These findings offer valuable insights for novel uses of this plant biomass in the future.
... Furthermore, with the release of the complete P. patens genome sequence (Rensing et al., 2008), precise and efficient genetic manipulation to explore biological functions of genes responsible for the unique features of the moss has become possible (Cove et al., 2009a). Subsequently, several studies have reported the development of powerful bioengineering tools for the production of high-value compounds in mosses, such as terpenoids, biopharmaceuticals, and cosmetic products (Bach et al., 2014;Reski et al., 2015;Wandrey et al., 2018). ...
Mosses number about 13,000 species and are an important resource for the study of the plant evolution that occurred during terrestrial colonization by plants. Recently, the physiological and metabolic characteristics that distinguish mosses from terrestrial plants have received attention. In the Arctic, in particular, mosses developed their own distinct physiological features to adapt to the harsh environment. However, little is known about the molecular mechanisms by which Arctic mosses survive in extreme environments due to the lack of basic knowledge and tools such as genome sequences and genetic transfection methods. In this study, we report the axenic cultivation and transfection of Arctic Bryum sp. KMR5045, as a model for bioengineering of Arctic mosses. We also found that the inherent low-temperature tolerance of KMR5045 permitted it to maintain slow growth even at 2°C, while the model moss species Physcomitrium patens failed to grow at all, implying that KMR5045 is suitable for studies of cold-tolerance mechanisms. To achieve genetic transfection of KMR5045, some steps of the existing protocol for P. patens were modified. First, protoplasts were isolated using 1% driselase solution. Second, the appropriate antibiotic was identified and its concentration was optimized for the selection of transfectants. Third, the cell regeneration period before transfer to selection medium was extended to 9 days. As a result, KMR5045 transfectants were successfully obtained and confirmed transfection by detection of intracellular Citrine fluorescence derived from expression of a pAct5:Citrine transgene construct. This is the first report regarding the establishment of a genetic transfection method for an Arctic moss species belonging to the Bryaceae. The results of this study will contribute to understanding the function of genes involved in environmental adaptation and to application for production of useful metabolites derived from stress-tolerant mosses.
Sustainable utilization of bioresources is the need of the hour that supports ecosystem and human wellbeing. Overexploitation of bioresource leads to catastrophic ecological processes like loss of habitat, which lead to irrecoverable loss of biological diversity. The biodiversity loss and unregulated ecosystem services result in sabotaging the declared UN Sustainable Development Goals. Many grassroots, and national and international studies provide mounting estimates of the overall gain delivered from the biological resources and ecological services. The global ecosystem services reveal a benefit of approximately 125–140 trillion USD/annum. There has been growing interest in lower group plant species in the last few decades as sources of novel nutraceuticals, pharmacologically active ingredients, or other economically valuable products. This chapter accounts for an insight into the utilization of bacteria, algae, fungi, lichens, bryophytes, pteridophytes, and gymnosperms and their bioactive molecules in ethnic medicine, trade of such bioresources with biopharmaceutical industries, and food or other industries. Unhealthy utilization accelerates the extinction rate of many living organisms. Peoples participatory policy formulations connected with biodiversity conservation and economic growth will helps to soothe environmental derailment and loss of biowealth from the earth.KeywordsLower group plantsBioresourcesActive ingredientsEconomic benefits
The first moss-made drug candidate successfully passed clinical trial phase I.
A genetically engineered fragrant moss is on the market.
A bioactive ingredient from a moss is on the market for the cosmetic industry.
Peat-moss farming will help to halt greenhouse gas emissions.
Biotechnological exploitation of mosses has several aspects, for example, the use of moss extracts or the whole plant for diverse industrial applications as well as their employment as production platforms for valuable metabolites or pharmaceutical proteins, especially using the genetically and developmentally best-characterised model moss Physcomitrella patens. Whole moss plants, in particular peat mosses (Sphagnum spec.), are useful for environmental approaches, biomonitoring of environmental pollution and CO2-neutral ‘farming’ on rewetted bogs to combat climate change. In addition, the lifestyle of mosses suggests the evolution of genes necessary to cope with biotic and abiotic stress situations, which could be applied to crop plants, and their structural features bear an inspiring potential for biomimetics approaches.
Mosses, dominant elements in the vegetation of polar and alpine regions, have well-developed stress tolerance features permitting cryptobiosis. However, direct regeneration after longer periods of cryptobiosis has been demonstrated only from herbarium and frozen material preserved for 20 years at most [1]. Recent field observations of new moss growth on the surface of small moss clumps re-exposed from a cold-based glacier after about 400 years of ice cover have been accompanied by regeneration in culture from homogenised material [2], but there are no reported instances of regrowth occurring directly from older preserved material.
The nuclear lamina consists of A- and B-type lamins. Mutations in LMNA cause many human diseases, including progeria, a premature aging syndrome, whereas LMNB1 duplication causes adult-onset autosomal dominant leukodystrophy (ADLD). LMNB1 is reduced in cells from progeria patients, but the significance of this reduction is unclear. In this paper, we show that LMNB1 protein levels decline in senescent human dermal fibroblasts and keratinocytes, mediated by reduced transcription and inhibition of LMNB1 messenger ribonucleic acid (RNA) translation by miRNA-23a. This reduction is also observed in chronologically aged human skin tissue. To determine whether altered LMNB1 levels cause senescence, we either increased or reduced LMNB1. Both LMNB1 depletion and overexpression inhibited proliferation, but only LMNB1 overexpression induced senescence, which was prevented by telomerase expression or inactivation of p53. This phenotype was exacerbated by a simultaneous reduction of LMNA/C. Our results demonstrate that altering LMNB1 levels inhibits proliferation and are relevant to understanding the molecular pathology of ADLD.
The number of pore complexes per nucleus was determined for a wide variety of cultured cells selected for their variable DNA content over a range of 1-5,6000. The pore number was compared to DNA content, nuclear surface area, and nuclear volume. Values for pore frequency (pores/square micrometer) were relatively constant in the species studied. When the pore to DNA ratio was plotted against the DNA content, there was a remarkable correlation which decreased exponentially for the cells of vertebrae origin. Exceptions were the heteroploid mammalian cells which had the same ratio as the diploid mammalian cells despite higher DNA content.
The results are interpreted to mean that neither the nuclear surface, the nuclear volume, nor the DNA content alone determines the pore number of the nucleus, but rather an as yet undetermined combination of different factors. The surface and volume of vertebrate nuclei do not decrease with decreasing DNA content below a given value. The following speculation is suggested to account for the anomalous size changes of the nucleus relative to DNA content in vertebrates. Species with small DNA complements have a relatively large proportion of active chromatin which determines the limits of the physical parameters of the nucleus. The amount of active chromatin maybe the same for at least the vertebrates with low DNA content, At high DNA content, the nuclear parameters may be determined by the relatively high proportion of inactive condensed chromatin which increases the nuclear surface and volume.
A major transitional step in Earth’s history was the conquest of land by plants, which fundamentally changed carbon cycling and elevated oxygen levels. In a moss model of early land plants, three out of six MIKCC-type MADS-box transcription factors ensure external water conduction and the function of motile sperm.
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons in the brain and spinal cord. The hallmark pathological feature in most cases of ALS is nuclear depletion and cytoplasmic accumulation of the protein TDP-43 in degenerating neurons. Consistent with this pattern of intracellular protein redistribution, impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to ALS pathology. Dysfunction in nucleocytoplasmic transport is also an emerging theme in physiological aging and other related neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. Here we review transport through the nuclear pore complex, pointing out vulnerabilities that may underlie ALS and potentially contribute to this and other age-related neurodegenerative diseases.
Lignin, one of the most abundant biopolymers on Earth, derives from the plant phenolic metabolism. It appeared upon terrestrialization and is thought critical for plant colonization of land. Early diverging land plants do not form lignin, but already have elements of its biosynthetic machinery. Here we delete in a moss the P450 oxygenase that defines the entry point in angiosperm lignin metabolism, and find that its pre-lignin pathway is essential for development. This pathway does not involve biochemical regulation via shikimate coupling, but instead is coupled with ascorbate catabolism, and controls the synthesis of the moss cuticle, which prevents desiccation and organ fusion. These cuticles share common features with lignin, cutin and suberin, and may represent the extant representative of a common ancestor. Our results demonstrate a critical role for the ancestral phenolic metabolism in moss erect growth and cuticle permeability, consistent with importance in plant adaptation to terrestrial conditions.
Aging is a major risk factor for many human diseases, and in vitro generation of human neurons is an attractive approach for modeling aging-related brain disorders. However, modeling aging in differentiated human neurons has proved challenging. We generated neurons from human donors across a broad range of ages, either by iPSC-based reprogramming and differentiation or by direct conversion into induced neurons (iNs). While iPSCs and derived neurons did not retain aging-associated gene signatures, iNs displayed age-specific transcriptional profiles and revealed age-associated decreases in the nuclear transport receptor RanBP17. We detected an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC in young cells, while iPSC rejuvenation restored NCC in aged cells. These results show that iNs retain important aging-related signatures, thus allowing modeling of the aging process in vitro, and they identify impaired NCC as an important factor in human aging.
The mechanism of facilitated translocation through nuclear pore complexes (NPCs) is only poorly understood. Here, we present a kinetic analysis of the process using various model substrates. We find that the translocation capacity of NPCs is unexpectedly high, with a single NPC allowing a mass flow of nearly 100 MDa/s and rates in the order of 10(3) translocation events per second. Our data further indicate that high affinity interactions between the translocation substrate and NPC components are dispensable for translocation. We propose a 'selective phase model' that could explain how NPCs function as a permeability barrier for inert molecules and yet become selectively permeable for nuclear transport receptors and receptor-cargo complexes.