Ending Aging

If you are looking for an accessible description of SENS research, our Chief Science Officer, Dr Aubrey de Grey, together with co-author Michael Rae, has written a book entitled Ending Aging. The book speaks to a broad audience, but it does so without 'dumbing down' the science at all. It is the ideal resource for either the biologist or the non-biologist, whether encountering SENS for the first time or wishing to absorb more of its details. Copies are available from your local bookstore or from Amazon.com. The details are: de Grey ADNJ, Rae M. Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. New York, NY: St. Martin's Press, 2007, 416pp, hardcover, ISBN 0-312-36706-6; or there is a paperback edition with an additional chapter covering more recent developments, ISBN 0-312-36707-4.


The following list of publications presents, by default, work funded in whole or in part by SENS Research Foundation. To view a much more extensive list of papers relevant to our work, including all papers cited in Ending Aging, alter the value of the "SRF Funded?" filter below.

  1. Akman K, Haaf T, Gravina S, Vijg J, Tresch A. Genome-wide quantitative analysis of DNA methylation from bisulfite sequencing data. Bioinformatics. 2014 Mar 27. [Epub ahead of print] PubMed: 24618468.

    Genome-wide quantitative analysis of DNA methylation from bisulfite sequencing data.

    Bioinformatics. 2014 Mar 27. [Epub ahead of print]

    Genome-wide quantitative analysis of DNA methylation from bisulfite sequencing data.

    Akman K, Haaf T, Gravina S, Vijg J, Tresch A.

    Abstract

    Abstract:

    SUMMARY:

    Here we present the open-source R/Bioconductor software package BEAT (BS-Seq Epimutation Analysis Toolkit). It implements all bioinformatics steps required for the quantitative high-resolution analysis of DNA methylation patterns from bisulfite sequencing data, including the detection of regional epimutation events, i.e. loss or gain of DNA methylation at CG positions relative to a reference. Using a binomial mixture model, the BEAT package aggregates methylation counts per genomic position, thereby compensating for low coverage, incomplete conversion and sequencing errors.

    AVAILABILITY AND IMPLEMENTATION:

    BEAT is freely available as part of Bioconductor at www.bioconductor.org/packages/devel/bioc/html/BEAT.html. The package is distributed under the GNU Lesser General Public License 3.0.

  2. Bains, William More than genes and cells: drug discovery in the ECM Drug Discovery World. 2013/14 Winter:65-70 Categories: GlycoSENS

    More than genes and cells: drug discovery in the ECM

    Drug Discovery World. 2013/14 Winter:65-70

    More than genes and cells: drug discovery in the ECM

    Bains, William

    Abstract

    Abstract:

    Drug discovery in the last few decades has focused on the cellular and genetic mechanisms of disease. This has been very successful in cancer, which is a disease of somatic genetics, and moderately successful elsewhere. But the declining productivity of pharmaceutical and biotechnology investment in drug discovery and development suggests that we should be alert to other approaches. One is to look outside the cell, at the extracellular superstructure of the body. Once viewed as an inert structure that is just the biological equivalent of a petri dish, the extracellular milieu is now being seen as a therapeutic target, especially for diseases of old age. Importantly, targeting the scaffold of the body might be a much faster route to treatment for some conditions than attempting to find, and fix, underlying cellular or genetic aetiology of disease.

  3. BM Davies, SR Rikabi, A French, R Pinedo-Villanueva, ME Morrey, K Wartolowska, DA Brindley Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study J Tissue Eng. 2014 Jan-Dec. (Epub ahead of print). doi:10.1177/2041731414551764 Categories: Socioethical

    Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study

    J Tissue Eng. 2014 Jan-Dec. (Epub ahead of print). doi:10.1177/2041731414551764

    Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study

    BM Davies, SR Rikabi, A French, R Pinedo-Villanueva, ME Morrey, K Wartolowska, DA Brindley

    Abstract

    Abstract:

    There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

  4. Bonnet C, Kaltimbacher V, Ellouze S, Augustin S, Bénit P, Forster V, Rustin P, Sahel JA, Corral-Debrinski M. Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or V subunits. Rejuvenation Res 2007;10(2):127-144. PubMed: 17518546. Categories: MitoSENS

    Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or V subunits.

    Rejuvenation Res 2007;10(2):127-144.

    Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or V subunits.

    Bonnet C, Kaltimbacher V, Ellouze S, Augustin S, Bénit P, Forster V, Rustin P, Sahel JA, Corral-Debrinski M.

    Abstract

    Abstract:

    The possibility of synthesizing mitochondrial DNA (mtDNA)-coded proteins in the cytosolic compartment, called allotopic expression, provides an attractive option for genetic treatment of human diseases caused by mutations of the corresponding genes. However, it is now appreciated that the high hydrophobicity of proteins encoded by the mitochondrial genome represents a strong limitation on their mitochondrial import when translated in the cytosol. Recently, we optimized the allotopic expression of a recoded ATP6 gene in human cells, by forcing its mRNA to localize to the mitochondrial surface. In this study, we show that this approach leads to a long-lasting and complete rescue of mitochondrial dysfunction of fibroblasts harboring the neurogenic muscle weakness, ataxia and retinitis Pigmentosa T8993G ATP6 mutation or the Leber hereditary optic neuropathy G11778A ND4 mutation. The recoded ATP6 gene was associated with the cis-acting elements of SOD2, while the ND4 gene was associated with the cis-acting elements of COX10. Both ATP6 and ND4 gene products were efficiently translocated into the mitochondria and functional within their respective respiratory chain complexes. Indeed, the abilities to grow in galactose and to produce adenosine triphosphate (ATP) in vitro were both completely restored in fibroblasts allotopically expressing either ATP6 or ND4. Notably, in fibroblasts harboring the ATP6 mutation, allotopic expression of ATP6 led to the recovery of complex V enzymatic activity. Therefore, mRNA sorting to the mitochondrial surface represents a powerful strategy that could ultimately be applied in human therapy and become available for an array of devastating disorders caused by mtDNA mutations.

  5. Boura JS, Vance M, Yin W, Madeira C, Lobato da Silva C, Porada CD, Almeida-Porada G Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells Mol Ther Methods Clin Dev. 2014 Sep;2014(1). pii: 14041 PubMed: 25279386. Categories: OncoSENS, RepleniSENS

    Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells

    Mol Ther Methods Clin Dev. 2014 Sep;2014(1). pii: 14041

    Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells

    Boura JS, Vance M, Yin W, Madeira C, Lobato da Silva C, Porada CD, Almeida-Porada G

    Abstract

    Abstract:

    Mesenchymal stromal cells (MSC) constitutively express low levels of human leukocyte antigen-G (HLA-G), which has been shown to contribute to their immunomodulatory and anti-inflammatory properties. Here, we hypothesized that overexpression of HLA-G on bone marrow-derived MSC would improve their immunomodulatory function, thus increasing their therapeutic potential. Therefore, we investigated which gene transfer system is best suited for delivering this molecule while maintaining its immuno-modulatory effects. We performed a side-by-side comparison between three nonviral plasmid-based platforms (pmax-HLA-G1; MC-HLA-G1; pEP-HLA-G1) and a viral system (Lv-HLA-G1) using gene transfer parameters that yielded similar levels of HLA-G1-expressing MSC. Natural killer (NK) cell-mediated lysis assays and T cell proliferation assays showed that MSC modified with the HLA-G1 expressing viral vector had significantly lower susceptibility to NK-lysis and significantly reduced T cell proliferation when compared to nonmodified cells or MSC modified with plasmid. We also show that, in plasmid-modified MSC, an increase in Toll-like receptor (TLR)9 expression is the mechanism responsible for the abrogation of HLA-G1's immunomodulatory effect. Although MSC can be efficiently modified to overexpress HLA-G1 using viral and nonviral strategies, only viral-based delivery of HLA-G1 is suitable for improvement of MSC's immunomodulatory properties.

  6. Brindley D, Davie N Regenerative Medicine Through a Crisis: Social Perception and the Financial Reality. Rejuvenation Research 2009, 12(6): 455-461 PubMed: 20041739. Categories: Socioethical

    Regenerative Medicine Through a Crisis: Social Perception and the Financial Reality.

    Rejuvenation Research 2009, 12(6): 455-461

    Regenerative Medicine Through a Crisis: Social Perception and the Financial Reality.

    Brindley D, Davie N

    Abstract

    Abstract:

    The aim of this perspective piece is to highlight how the “social perception” and “financial reality” of regenerative medicine may act to hinder its evolution into the principal health-care option for the future. We also consider the role of the consumer and the need for increased public awareness. Furthermore, we consider the effects of the changing social attitudes toward the field, as well as taking into account the influence of current and future political thinking. From a financial viewpoint, we analyze the compatibility of the current venture capital model with regenerative medicine start-ups and explore approaches to ensure sufficient funding and support throughout all stages of product development, for example, the modularization of funding.

  7. Brindley DA, Barker RW, Lachmann PJ Better drug access for terminal patients Nature. 2013 Oct 3;502(7469):38. doi: 10.1038/502038c PubMed: 24091972.

    Better drug access for terminal patients

    Nature. 2013 Oct 3;502(7469):38. doi: 10.1038/502038c

    Better drug access for terminal patients

    Brindley DA, Barker RW, Lachmann PJ

    Abstract

    Abstract:

    The late statistician Les Halpin was the founder of the Empower: Access to Medicine campaign to improve the availability of experimental therapies and to accelerate drug approval and licensing for people with life-threatening illnesses.  His campaign has enabled drugs to get to market faster and more cheaply.

  8. Brindley DA, French A, Suh J, Roberts M, Davies B, Pinedo-Villanueva R, Wartolowska K, Rooke K, Kramm A, Judge A, Morrey M, Chandra A, Hurley H, Grover L, Bingham I, Siegel B, Rattley MS, Buckler RL, McKeon D, Krumholz K, Hook L, May M, Rikabi S, Pigott R, Morys M, Sabokbar A, Titus E, Laabi Y, Lemaitre G, Zahkia R, Sipp D, Horne R, Bravery C, Williams D, Wall I, Snyder EY, Karp JM, Barker RW, Bure K, Carr AJ, Reeve B The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation Stem Cells Dev. 2013 Dec;22 Suppl 1:63-72. doi: 10.1089/scd.2013.0403 PubMed: 24304079.

    The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation

    Stem Cells Dev. 2013 Dec;22 Suppl 1:63-72. doi: 10.1089/scd.2013.0403

    The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation

    Brindley DA, French A, Suh J, Roberts M, Davies B, Pinedo-Villanueva R, Wartolowska K, Rooke K, Kramm A, Judge A, Morrey M, Chandra A, Hurley H, Grover L, Bingham I, Siegel B, Rattley MS, Buckler RL, McKeon D, Krumholz K, Hook L, May M, Rikabi S, Pigott R, Morys M, Sabokbar A, Titus E, Laabi Y, Lemaitre G, Zahkia R, Sipp D, Horne R, Bravery C, Williams D, Wall I, Snyder EY, Karp JM, Barker RW, Bure K, Carr AJ, Reeve B

    Abstract

    Abstract:

    Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.

     

  9. Brindley DA, French AL, Baptista R, Timmins N, Adams T, Wall I, Bure K Cell Therapy Bioprocessing Technologies and Indicators of Technological Convergence BioProcess International 12(3)s (March 2014)

    Cell Therapy Bioprocessing Technologies and Indicators of Technological Convergence

    BioProcess International 12(3)s (March 2014)

    Cell Therapy Bioprocessing Technologies and Indicators of Technological Convergence

    Brindley DA, French AL, Baptista R, Timmins N, Adams T, Wall I, Bure K

    Abstract

    Abstract:

    The cell therapy industry is undergoing a natural evolution from scientific curiosity into a commercially and clinically attractive opportunity (1). This evolution is by no means complete, and growing evidence suggests that its progression is driving significant developments in cell therapy bioprocessing — notably, convergence.

  10. Brindley DA, Wall IB, Bure K. Automation of Cell Therapy Biomanufacturing: Minimizing Regulatory Risks and Maximising Return on Investment Bioprocess International, Supplement; vol. 11, No. S3, March 2013, pp. 18–25.


    Automation of Cell Therapy Biomanufacturing: Minimizing Regulatory Risks and Maximising Return on Investment

    Bioprocess International, Supplement; vol. 11, No. S3, March 2013, pp. 18–25.


    Automation of Cell Therapy Biomanufacturing: Minimizing Regulatory Risks and Maximising Return on Investment

    Brindley DA, Wall IB, Bure K.

    Abstract

    Abstract:

    (No abstract available.)

  11. Brindley DA, Wall IB. The Commercial Manufacture of Cell Therapies In: Standardization in Cell and Tissue Engineering: Methods and Protocols (V. Salih, ed.) Woodhead Publishing, 2012, pp. 212-240.

    The Commercial Manufacture of Cell Therapies

    In: Standardization in Cell and Tissue Engineering: Methods and Protocols (V. Salih, ed.) Woodhead Publishing, 2012, pp. 212-240.

    The Commercial Manufacture of Cell Therapies

    Brindley DA, Wall IB.

    Abstract

    Abstract:

    (No abstract available.)

  12. Bussel II, Stupple A, Moody KJ, Lefkowitz DM. Call to action: medical students for regenerative medicine. Rejuvenation Res. 2010 Feb;13(1):1-2. PubMed: 20230272. Categories: Introductions

    Call to action: medical students for regenerative medicine.

    Rejuvenation Res. 2010 Feb;13(1):1-2.

    Call to action: medical students for regenerative medicine.

    Bussel II, Stupple A, Moody KJ, Lefkowitz DM.

    Abstract

    Abstract:
  13. Chen Y, Ma X, Zhang M, Wang X, Wang C, Wang H, Guo P, Yuan W, Rudolph KL, Zhan Q, Ju Z. Gadd45a regulates hematopoietic stem cell stress responses in mice. Blood. 2014 Feb 6;123(6):851-62. doi: 10.1182/blood-2013-05-504084. PubMed: 24371210.

    Gadd45a regulates hematopoietic stem cell stress responses in mice.

    Blood. 2014 Feb 6;123(6):851-62. doi: 10.1182/blood-2013-05-504084.

    Gadd45a regulates hematopoietic stem cell stress responses in mice.

    Chen Y, Ma X, Zhang M, Wang X, Wang C, Wang H, Guo P, Yuan W, Rudolph KL, Zhan Q, Ju Z.

    Abstract

    Abstract:

    Gadd45a has been involved in DNA damage response and in many malignancies, including leukemia. However, the function of Gadd45a in hematopoietic stem cells (HSCs) remains unknown. Here, we reported that Gadd45a-deficient (Gadd45a(-/-)) mice showed a normal hematologic phenotype under homeostatic conditions. However, following 5-fluorouracil treatment, Gadd45a(-/-) HSCs exhibited a faster recovery, associated with an increase in the proliferation rate. Interestingly, young Gadd45a(-/-) HSCs showed enhanced reconstitution ability in serial transplantation. Following ionizing radiation (IR), young Gadd45a(-/-) HSCs exhibited an increased resistance to IR-induced DNA damage, associated with a decrease in the apoptosis rate and delayed DNA repair. The significantly higher level of DNA damage in Gadd45a(-/-) HSCs ultimately promoted B-cell leukemia in further transplanted recipient mice. In old mice, Gadd45a(-/-) HSCs were functionally equal to wild-type HSCs but exhibited more DNA damage accumulation and increased sensitivity to IR than wild-type HSCs. In conclusion, Gadd45a plays a significant role in HSC stress responses. Gadd45a deficiency leads to DNA damage accumulation and impairment in apoptosis after exposure to IR, which increases the susceptibility of leukemogenesis.

  14. Chen Y, Yang R, Guo P, Ju Z. Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice. Protein Cell. 2014 Jan;5(1):80-9. doi: 10.1007/s13238-013-0017-9. PubMed: 24474198.

    Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice.

    Protein Cell. 2014 Jan;5(1):80-9. doi: 10.1007/s13238-013-0017-9.

    Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice.

    Chen Y, Yang R, Guo P, Ju Z.

    Abstract

    Abstract:

    Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.

  15. Corral-Debrinski M. mRNA specific subcellular localization represents a crucial step for fine-tuning of gene expression in mammalian cells. Biochim Biophys Acta. 2007 Apr;1773(4):473-5. PubMed: 17292980. Categories: MitoSENS

    mRNA specific subcellular localization represents a crucial step for fine-tuning of gene expression in mammalian cells.

    Biochim Biophys Acta. 2007 Apr;1773(4):473-5.

    mRNA specific subcellular localization represents a crucial step for fine-tuning of gene expression in mammalian cells.

    Corral-Debrinski M.

    Abstract

    Abstract:

    mRNA subcellular distribution and translational control are key player mechanisms for post-transcriptional gene expression regulation. In the last decade it has become increasingly clear that these processes are associated with various human diseases. Understanding the interconnected multistep process of mRNA localization and its involvement in organelle biogenesis and in the overall spatial structure of eukaryotic cells will be an important step towards the long-term goal of curing individual molecular defects. In a recent issue, Russo et al. [The 3'-untranslated region directs ribosomal protein-encoding mRNAs to specific cytoplasmic regions, Biochim. Biophys. Acta, Mol. Cell Res. 1763 (8) (2006) 833-843] reported interesting findings on the mechanisms that direct mRNAs encoding different ribosomal proteins to specific cytoplasmic regions in human cells.

  16. de Grey ADNJ A Mechanism Proposed to Explain the Rise in Oxidative Stress During Aging J Anti-Aging Med. 1998 Spring. 1(1): 53-66. doi:10.1089/rej.1.1998.1.53. Categories: MitoSENS

    A Mechanism Proposed to Explain the Rise in Oxidative Stress During Aging

    J Anti-Aging Med. 1998 Spring. 1(1): 53-66. doi:10.1089/rej.1.1998.1.53.

    A Mechanism Proposed to Explain the Rise in Oxidative Stress During Aging

    de Grey ADNJ

    Abstract

    Abstract:

    Most phenotypes of aging in vertebrates may be caused by a progressive decline in the ability of antioxidant defences to maintain cellular and systemic homeostasis. This is due both to a diminished efficacy of those defences and to an enhanced level of pro-oxidant toxicity; the imbalance between the two has been termed oxidative stress. However, the cause of this increasing imbalance remains obscure. This article proposes a mechanism by which spontaneously mutant mitochondrial DNA (mtDNA), despite being present only in very small quantities in the body, may be the main generator of oxidative stress. Mutant mtDNA is distributed very unevenly within a tissue: some cells apparently contain no wild-type mtDNA whatever. Those cells must rely on glycolysis for ATP production; furthermore, they require a system to stabilize their NAD+/NADH ratio. This can only be achieved by an efflux of electrons from the cell, most probably mediated by the plasma membrane oxidoreductase (PMOR). It is proposed that the required rate of electron efflux from these anaerobic cells exceeds the local electron-accepting capacity of "safe" acceptors in plasma such as dehydroascorbate, with the result that reactive species, such as Superoxide, are formed. This leads to increased oxidation of lipids in the plasma, notably of low-density lipoprotein (LDL) particles, which are subsequently imported into mitochondrially healthy cells. This oxidized lipoprotein must be destroyed by the recipient cells' antioxidant defences. That task diverts the cell from the degradation of pro-oxidants that it is itself generating; thus, it imposes oxidative stress on the cell. As the number of anaerobic cells in the body rises, so does oxidative stress in all cells. The consistency of this hypothesis with known facts is discussed, and technically feasible tests are suggested both of the proposed mechanism and of its overall contribution to mammalian aging, including plausible interventions to retard the process.

  17. Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, Kung S, Jiang KP, Conboy IM. Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nat Commun. 2014 Jun 10;5:4082. doi: 10.1038/ncomms5082. PubMed: 24915299. Categories: RepleniSENS

    Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration.

    Nat Commun. 2014 Jun 10;5:4082. doi: 10.1038/ncomms5082.

    Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration.

    Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, Kung S, Jiang KP, Conboy IM.

    Abstract

    Abstract:

    The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation; however, systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin-a hormone best known for its role in lactation, parturition and social behaviours-is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signalling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation through activation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle but instead leads to premature sarcopenia. Considering that oxytocin is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle ageing.

  18. Ellouze S, Augustin S, Bouaita A, Bonnet C, Simonutti M, Forster V, Picaud S, Sahel JA, Corral-Debrinski M. Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. Am J Hum Genet. 2008 Sep;83(3):373-87. doi: 10.1016/j.ajhg.2008.08.013. PubMed: 18771762. Categories: MitoSENS

    Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction.

    Am J Hum Genet. 2008 Sep;83(3):373-87. doi: 10.1016/j.ajhg.2008.08.013.

    Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction.

    Ellouze S, Augustin S, Bouaita A, Bonnet C, Simonutti M, Forster V, Picaud S, Sahel JA, Corral-Debrinski M.

    Abstract

    Abstract:

    Mitochondrial diseases due to mutations in mitochondrial DNA can no longer be ignored in most medical areas. With prevalence certainly higher than one in 6000, they probably represent the most common form of metabolic disorders. Despite progress in identification of their molecular mechanisms, little has been done with regard to therapy. We have recently optimized the allotopic expression for the mitochondrial genes ATP6, ND1, and ND4 and obtained a complete and long-lasting rescue of mitochondrial dysfunction in the human fibroblasts in which these genes were mutated. However, biosafety and benefit to mitochondrial function must be validated in animal models prior to clinical applications. To create an animal model of Leber Hereditary Optic Neuropathy (LHON), we introduced the human ND4 gene harboring the G11778A mutation, responsible of 60% of LHON cases, to rat eyes by in vivo electroporation. The treatment induced the degeneration of retinal ganglion cells (RGCs), which were 40% less abundant in treated eyes than in control eyes. This deleterious effect was also confirmed in primary cell culture, in which both RGC survival and neurite outgrowth were compromised. Importantly, RGC loss was clearly associated with a decline in visual performance. A subsequent electroporation with wild-type ND4 prevented both RGC loss and the impairment of visual function. Hence, these data provide the proof-of-principle that optimized allotopic expression can be an effective treatment for LHON, and they open the way to clinical studies on other devastating mitochondrial disorders.

  19. French A, Suh JY, Suh CY, Rubin L, Barker R, Bure K, Reeve B, Brindley DA Global strategic partnerships in regenerative medicine Trends Biotechnol. 2014 Sep;32(9):436-40. doi: 10.1016/j.tibtech.2014.05.007 PubMed: 25150363 . Categories: Socioethical

    Global strategic partnerships in regenerative medicine

    Trends Biotechnol. 2014 Sep;32(9):436-40. doi: 10.1016/j.tibtech.2014.05.007

    Global strategic partnerships in regenerative medicine

    French A, Suh JY, Suh CY, Rubin L, Barker R, Bure K, Reeve B, Brindley DA

    Abstract

    Abstract:

    The approach to research and development in biomedical science is changing. Increasingly, academia and industry seek to collaborate, and share resources and expertise, by establishing partnerships. Here, we explore the co-development partnership landscape in the field of regenerative medicine, focusing on agreements involving one or more private entities. A majority of the largest biopharmaceutical companies have announced strategic partnerships with a specific regenerative medicine focus, signifying the growth and widening appeal of this emerging sector.

  20. French AL, Bure K, Brindley DA CASMI TSCC Launch Event, Paris, France, July 2013: An Assessment of the Key Barriers to the Commercialization and Clinical Adoption of Pluripotent Stem Cell Therapies Rejuvenation Res. February 2014, 17(1): 84-88. doi:10.1089/rej.2014.1545 PubMed: 24392658.

    CASMI TSCC Launch Event, Paris, France, July 2013: An Assessment of the Key Barriers to the Commercialization and Clinical Adoption of Pluripotent Stem Cell Therapies

    Rejuvenation Res. February 2014, 17(1): 84-88. doi:10.1089/rej.2014.1545

    CASMI TSCC Launch Event, Paris, France, July 2013: An Assessment of the Key Barriers to the Commercialization and Clinical Adoption of Pluripotent Stem Cell Therapies

    French AL, Bure K, Brindley DA

    Abstract

    Abstract:

    The high incidence of unmet medical needs in combination with the rising burden of chronic diseases, linked to an increasingly aging population, necessitates new approaches to therapeutic intervention. One potential class of health care innovation that may offer an alternative approach to addressing current shortfalls is stem cell therapies. The CASMI Translational Stem Cell Consortium (CTSCC) was formed to elucidate the key hurdles to the commercialization and clinical adoption of stem cell technologies, with a particular focus on pluripotent stem cell (PSC) technologies. As a global pre-competitive academic–industry consortium, the CTSCC unites thought leaders from a range of sectors and technical specialties in defining and discovering solutions to roadblocks that will impede the field. Targeted toward stakeholder requirements at the delivery end of the translational spectrum, the CTSCC aims to provide mechanisms for multidirectional dialogue and to produce academically rigorous and commercially practicable research outputs to accelerate industry progress. On the 30th and 31st of July, 2013, the CASMI Translational Stem Cell Consortium (CTSCC) held a launch event at the Saint James Club, Paris, France.

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