在新出版的Nature Genetics杂志上，新加坡和德国的科学家发现， PYCR1基因发生突变将导致皮肤过早衰老，也称之为”皱皮综合症(wrinkly skin syndrome)”。这项发现不仅说明了PYCR1蛋白质水平升高可以缓解快速衰老、皮肤皱缩症状，而且还发现了某些基因与保持肌肤年轻态有关。
研究人员Bruno Reversade及其课题组利用生物信息学工具，分析了患“皱皮综合症”患者的DNA样品的信息。研究人员发现患者的17号染色体PYCR1基因发生缺陷，并且发现该基因发生某些特异性突变会导致老年人皮肤松弛，估量丢失，快关节脱位以及白内障。
他们还研究了皱皮综合症患者的皮肤和骨骼，这两种组织受该疾病的影响最严重。在正常条件下，皮肤和骨骼中含有较高水平的PYCR1蛋白，因此，正对提高PYCR1蛋白活性水平的疗法或许能够减缓衰老的过程。
PYCR1蛋白位于线粒体内。在试验中，研究人员观察到PYCR1突变体中线粒体形态的变化以及结缔组织中细胞死亡。为了确定PYCR1蛋白减少对机体产生的影响，研究人员利用基因工程手段关闭模式生物青蛙和鱼的PYCR1基因，再研究它们的生长状况。他们发现，这些动物皮肤的线粒体功能发生改变，细胞死亡量增加。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics 41, 1016 - 1021 (2009) 2 August 2009 | doi:10.1038/ng.413
Mutations in PYCR1 cause cutis laxa with progeroid features
Bruno Reversade1,33, Nathalie Escande-Beillard1,33, Aikaterini Dimopoulou2, Bj?rn Fischer2, Serene C Chng1, Yun Li3, Mohammad Shboul1, Puay-Yoke Tham1, Hülya Kayserili4, Lihadh Al-Gazali5, Monzer Shahwan6, Francesco Brancati7,8, Hane Lee9, Brian D O'Connor9, Mareen Schmidt-von Kegler2,10, Barry Merriman9, Stanley F Nelson9, Amira Masri11, Fawaz Alkazaleh11, Deanna Guerra12, Paola Ferrari13, Arti Nanda14, Anna Rajab15, David Markie16, Mary Gray16, John Nelson17, Arthur Grix18, Annemarie Sommer19, Ravi Savarirayan20, Andreas R Janecke21, Elisabeth Steichen22, David Sillence23, Ingrid Hauer24, Birgit Budde25, Gudrun Nürnberg25, Peter Nürnberg25, Petra Seemann10,26, Désirée Kunkel26, Giovanna Zambruno27, Bruno Dallapiccola7, Markus Schuelke28, Stephen Robertson29, Hanan Hamamy6, Bernd Wollnik3,30,31, Lionel Van Maldergem32, Stefan Mundlos2,10,26 & Uwe Kornak2,10
Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation1, 2, 3. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.
