Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, EX2 5DW, UK.
Institute of Biodiversity Animal Health & Comparative Medicine, University of Glasgow, G12 8QQ, UK.
Exp Gerontol. 2019 Dec;128:110736. doi: 10.1016/j.exger.2019.110736. Epub 2019 Sep 12.
Dietary restriction (DR) represents one of the most reproducible interventions to extend lifespan and improve health outcomes in a wide range of species, but substantial variability in DR response has been observed, both between and within species. The mechanisms underlying this variation in effect are still not well characterised. Splicing regulatory factors have been implicated in the pathways linked with DR-induced longevity in C. elegans and are associated with lifespan itself in mice and humans. We used qRT-PCR to measure the expression levels of a panel of 16 age- and lifespan-associated splicing regulatory factors in brain, heart and kidney derived from three recombinant inbred strains of mice with variable lifespan responses to short-term (2 months) or long-term (10 months) 40% DR to determine their relationship to DR-induced longevity. We identified 3 patterns of association; i) splicing factors associated with DR alone, ii) splicing factors associated with strain alone or iii) splicing factors associated with both DR and strain. Tissue specific variation was noted in response to short-term or long-term DR, with the majority of effects noted in brain following long-term DR in the positive responder strain TejJ89. Association in heart and kidney were less evident, and occurred following short-term DR. Splicing factors associated with both DR and strain may be mechanistically involved in strain-specific differences in response to DR. We provide here evidence concordant with a role for some splicing factors in the lifespan modulatory effects of DR across different mouse strains and in different tissues.
饮食限制（DR）是延长寿命和改善多种物种健康结果的最可重复的干预措施之一，但在不同物种之间和同一物种内，DR 反应的变异性很大。这种效应变化的机制仍未得到很好的描述。剪接调控因子已被牵涉到与 DR 诱导的秀丽隐杆线虫长寿相关的途径中，并且与小鼠和人类的寿命本身有关。我们使用 qRT-PCR 测量了来自三种重组近交系小鼠的大脑、心脏和肾脏中 16 个与年龄和寿命相关的剪接调控因子的表达水平，这些小鼠对短期（2 个月）或长期（10 个月）40%DR 的反应寿命不同，以确定它们与 DR 诱导的长寿之间的关系。我们确定了 3 种关联模式；i）与 DR 单独相关的剪接因子，ii）与菌株单独相关的剪接因子，或 iii）与 DR 和菌株都相关的剪接因子。短期或长期 DR 引起的组织特异性变化，在阳性应答株 TejJ89 中，长期 DR 后大脑中观察到大多数影响。在心脏和肾脏中的关联不太明显，并且发生在短期 DR 之后。与 DR 和菌株都相关的剪接因子可能在对 DR 的反应中具有机制上的菌株特异性差异。我们在此提供了证据，证明一些剪接因子在不同小鼠品系和不同组织中 DR 的寿命调节作用中具有作用。
