SIRT1, miR-132 and miR-212 link human longevity to Alzheimer's Disease.
SIRT1, miR-132 and miR-212 link human longevity to Alzheimer's Disease.
复制标题
DOI：
10.1038/s41598-018-26547-6
复制
发表时间：
2018-05-31
影响因子：
4.6
通讯作者：
Gurwitz D
中科院分区：
文献类型：
--
作者：
Hadar A;Milanesi E;Walczak M;Puzianowska-Kuźnicka M;Kuźnicki J;Squassina A;Niola P;Chillotti C;Attems J;Gozes I;Gurwitz D
阿尔茨海默病（AD）是老年痴呆症的最常见原因。百岁老人--年龄超过100岁，同时保持良好的认知能力--似乎具有独特的生物学特征，可以健康衰老并预防痴呆症。在此，我们研究了SIRT 1沿着miR-132和miR-212的表达，这两种已知调节SIRT 1的microRNA来自45名21至105岁的健康供体和24名AD患者的淋巴母细胞系（LCL），以及来自14名AD患者和20名年龄匹配的非痴呆个体的死后嗅球和海马组织。我们观察到，与年龄匹配的健康对照相比，AD患者LCL中SIRT 1的表达降低了4.0倍（P = 0.001），而miR-132（1.7倍; P = 0.014）和miR-212（2.1倍; P = 0.036）的表达相应较高。此外，与来自56-82岁个体的LCL相比，百岁LCL中的SIRT 1表达高2.2倍（P = 0.001）;而百岁LCL中的miR-132和miR-212的表达分别低7.6倍和4.1倍。在AD患者来源的LCL和死后AD嗅球和海马组织中观察到SIRT 1、miR-132和miR-212表达与认知评分的相关性，这表明较高的SIRT 1表达（可能由较低的miR-132和miR-212介导）可能保护老年个体免受痴呆，并反映在其外周组织中。
Alzheimer’s Disease (AD) is the most common cause of dementia in the elderly. Centenarians – reaching the age of >100 years while maintaining good cognitive skills – seemingly have unique biological features allowing healthy aging and protection from dementia. Here, we studied the expression of SIRT1 along with miR-132 and miR-212, two microRNAs known to regulate SIRT1, in lymphoblastoid cell lines (LCLs) from 45 healthy donors aged 21 to 105 years and 24 AD patients, and in postmortem olfactory bulb and hippocampus tissues from 14 AD patients and 20 age-matched non-demented individuals. We observed 4.0-fold (P = 0.001) lower expression of SIRT1, and correspondingly higher expression of miR-132 (1.7-fold; P = 0.014) and miR-212 (2.1-fold; P = 0.036), in LCLs from AD patients compared with age-matched healthy controls. Additionally, SIRT1 expression was 2.2-fold (P = 0.001) higher in centenarian LCLs compared with LCLs from individuals aged 56–82 years; while centenarian LCLs miR-132 and miR-212 indicated 7.6-fold and 4.1-fold lower expression, respectively. Correlations of SIRT1, miR-132 and miR-212 expression with cognitive scores were observed for AD patient-derived LCLs and postmortem AD olfactory bulb and hippocampus tissues, suggesting that higher SIRT1 expression, possibly mediated by lower miR-132 and miR-212, may protect aged individuals from dementia and is reflected in their peripheral tissues.
登录
查看更多内容
影响因子：
5.6
作者：
Eskildsen TV;Jeppesen PL;Schneider M;Nossent AY;Sandberg MB;Hansen PB;Jensen CH;Hansen ML;Marcussen N;Rasmussen LM;Bie P;Andersen DC;Sheikh SP
通讯作者：
Sheikh SP
影响因子：
16.2
作者：
Herskovits AZ;Guarente L
通讯作者：
Guarente L
影响因子：
14
作者：
通讯作者：
--
影响因子：
11.4
作者：
Kim, Dohoon;Nguyen, Minh Dang;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei
DOI：
10.1016/b978-0-12-803690-7.00012-0
发表时间：
2017-01-01
期刊：
NEUROPROTECTION IN ALZHEIMER'S DISEASE
影响因子：
--
作者：
Hadar, A.;Gozes, I.;Gurwitz, D.
通讯作者：
Gurwitz, D.