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.
原创： 十六点五 中山二院糖尿病足中心
糖尿病足的切口设计是糖尿病足局部脓肿及窦道治疗的第一步，也是最关键的一步之一，由于糖尿病足脓肿和窦道的多样性，以及糖尿病足病人全身情况的不一致，因此，要找到糖尿病足切口的设计规律比较困难，我们根据大量的临床实践，制定了以下的一些原则。
在上节中提到局部鉴别皮肤组织的“死活”是一个难题，有读者问有关在创面表面用“亚甲基蓝”染料染色来鉴别的问题，这种方法是一种比较古老的方法，对于相对较干净的伤口的效果比较好，对于严重感染的伤口容易出现误报，而且为了最大程度的保护足的结构和功能，一般采取蚕食性的方法进行清创，用这些染料染色后，反而有时候会干扰对肉芽组织生长的判断，容易造成清创过多的情况，因此，目前应用较少（也比较难得到有证书能够在临床应用的这种染料）。
针对“杨氏扩散”的特殊性、沿着窦道扩散的缺点及足部手术的原则，我们设计了一种沿着窦道行纵向切开的“刘氏切法”（图1），特点是：（1）沿着窦道做平行于足纵轴切开；（2）一般在窦道开口及窦道末端切开；（3）切口长度3-4CM；（4）足弓部足底边缘部的切口非常关键。
足底溃疡是糖尿病足治疗的难点。尤其是足跟。从理论上讲，足底的组织结构较足背要致密很多，其具有很强的对于损伤的防护及对于细菌感染的抵抗能力，即使在糖尿病状态下，也有一定的防御能力。
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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