Leonard Guarente,1,2, * David A. Sinclair,2,3 and Guido Kroemer2,4,5,6, *
1 Department of Biology, Massachusetts Institute for Technology, Cambridge, MA 02139
2 Academy for Healthspan and Lifespan Research (AHLR), New York, NY, USA
3 Blavatnik Institute, Genetics Department, Harvard Medical School, Boston, MA 02115, USA
4 Centre de Recherche des Cordeliers, Equipe labellise´ e par la Ligue contre le cancer, Universite´ Paris Cite´ , Sorbonne Universite´ , Inserm U1138, Institut Universitaire de France, Paris, France
5 Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France
6 Institut du Cancer Paris CARPEM, Department of Biology, Hoˆ pital Europe´ en Georges Pompidou, AP-HP, Paris, France
*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L.G.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (G.K.)
https://doi.org/10.1016/j.cmet.2023.12.007
SUMMARY
Here, we summarize the current knowledge on eight promising drugs and natural compounds that have been tested in the clinic: metformin, NAD+ precursors, glucagon-like peptide-1 receptor agonists, TORC1 inhibitors, spermidine, senolytics, probiotics, and anti-inflammatories. Multiple clinical trials have commenced to evaluate the efficacy of such agents against age-associated diseases including diabetes, cardiovascular disease, cancer, and neurodegenerative diseases. There are reasonable expectations that drugs able to decelerate or reverse aging processes will also exert broad disease-preventing or -attenuating effects. Hence, the outcome of past, ongoing, and future disease-specific trials may pave the way to the development of new anti-aging medicines. Drugs approved for specific disease indications may subsequently be repurposed for the treatment of organism-wide aging consequences.
Javier Ganz,1,2,3,8,9 Lovelace J. Luquette,4,8 Sara Bizzotto,1,2,3,5,8 Michael B. Miller,1,3,6 Zinan Zhou,1,2,3 Craig L. Bohrson,4
Hu Jin,4 Antuan V. Tran,4 Vinayak V. Viswanadham,4 Gannon McDonough,6 Katherine Brown,6 Yasmine Chahine,1
Brian Chhouk,1 Alon Galor,4 Peter J. Park,4,7,* and Christopher A. Walsh1,2,3,10,*
1 Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Department of Pediatrics, and Howard Hughes Medical Institute, Boston Childrens Hospital, Boston, MA 02115, USA
2 Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA
3 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
4 Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
5 Sorbonne Universite´ , Institut du Cerveau (Paris Brain Institute) ICM, Inserm, CNRS, Hoˆ pital de la Pitie´ Salpeˆ trie`re, 75013 Paris, France
6 Department of Pathology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02115, USA
7 Division of Genetics, Brigham and Womens Hospital, Boston, MA 02115, USA
8 These authors contributed equally
9 Present address: Merck Research Laboratories, Cambridge, MA 02142, USA
10 Lead contact
*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (P.J.P.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (C.A.W.)
https://doi.org/10.1016/j.cell.2024.02.025
Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed wholegenome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4–104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types accumulate somatic mutations linearly with age, oligodendrocytes accumulated sSNVs 81% faster than neurons and indels 28% slower than neurons. Correlation of mutations with single-nucleus RNA profiles and chromatin accessibility from the same brains revealed that oligodendrocyte mutations are enriched in inactive genomic regions and are distributed across the genome similarly to mutations in brain cancers. In contrast, neuronal mutations are enriched in open, transcriptionally active chromatin. These stark differences suggest an assortment of active mutagenic processes in oligodendrocytes and neurons.
创伤是指由于各种致伤因素导致的机体软组织、骨骼甚至内脏器官等等各个系统的损伤,创伤可以根据发生地点、受伤部位、受伤组织、致伤因素及皮肤完整程度进行分类。 按发生地点分为战争伤、工业伤、农业伤、交通伤、体育伤、生活伤等;按受伤部位分为颅脑创伤、胸部创伤、腹部创伤、各部位的骨折和关节脱位、手部伤等;按受伤类型分为骨折、脱位、脑震荡、器官破裂等;相邻部位同时受伤者称为联合伤(如胸腹联合伤);按受伤的组织或器官分类时,又可按受伤组织的深浅分为软组织创伤、骨关节创伤和内脏创伤。软组织创伤指皮肤、皮下组织和肌肉的损伤,也包括行于其中的血管和神经。单纯的软组织创伤一般较轻,但广泛的挤压伤可致挤压综合征。血管破裂大出血亦可致命。骨关节创伤包括骨折和脱位,并按受伤的骨或关节进一步分类并命名。如股骨骨折、肩关节脱位等。内脏创伤又可按受伤的具体内脏进行分类和命名。如脑挫裂伤、肺挫伤、肝破裂等。同一致伤原因引起两个以上部位或器官的创伤,称为多处伤或多发伤。按致伤因素,分为火器伤、切伤、刺伤、撕裂伤、挤压伤、扭伤、挫伤等。按皮肤完整程度,分为闭合性创伤、开放性创伤等。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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