Fat maintenance is a predictor of the murine lifespan response to dietary restriction.
Fat maintenance is a predictor of the murine lifespan response to dietary restriction.
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DOI：
10.1111/j.1474-9726.2011.00702.x
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发表时间：
2011-08
期刊：
影响因子：
7.8
通讯作者：
Nelson JF
中科院分区：
文献类型：
--
作者：
Liao CY;Rikke BA;Johnson TE;Gelfond JA;Diaz V;Nelson JF
饮食限制（DR）是最有效的延长寿命的方法之一，通常与减少肥胖有关。这种减少被认为是DR延长寿命效果的重要因素，因为过度肥胖与代谢和年龄相关疾病有关。先前，我们描述了41种重组近交系小鼠对DR的寿命反应的显著变化，从延长寿命到缩短寿命不等。在这里，我们使用这种变异来确定DR下寿命调节与脂肪减少的关系。在所有菌株中，DR寿命延长与脂肪减少呈负相关，在中年（雄性，r = - 0.41, P < 0.05, n = 38株；雌性，r = - 0.63, P < 0.001, n = 33株）和晚年测量。因此，脂肪减少最少的菌株更有可能延长寿命，而脂肪减少最多的菌株更有可能缩短寿命。我们发现了两个显著的数量性状位点（qtl）影响男性DR下的脂肪量，但没有一个影响寿命，从而排除了这些位点作为肥胖和寿命的协调调节因子的确认。我们的数据还为先前显示的影响DR下燃油效率的两个qtl提供了证据。总之，数据不支持DR在延长寿命中脂肪减少的重要作用。相反，与保持肥胖相关的因素对DR下的生存和延长寿命很重要。
Dietary restriction (DR), one of the most robust life-extending manipulations, is usually associated with reduced adiposity. This reduction is hypothesized to be important in the life-extending effect of DR, because excess adiposity is associated with metabolic and age-related disease. Previously, we described remarkable variation in the lifespan response of 41 recombinant inbred strains of mice to DR, ranging from life extension to life shortening. Here, we used this variation to determine the relationship of lifespan modulation under DR to fat loss. Across strains, DR life extension correlated inversely with fat reduction, measured at midlife (males, r = −0.41, P < 0.05, n = 38 strains; females, r = −0.63, P < 0.001, n = 33 strains) and later ages. Thus, strains with the least reduction in fat were more likely to show life extension, and those with the greatest reduction were more likely to have shortened lifespan. We identified two significant quantitative trait loci (QTLs) affecting fat mass under DR in males but none for lifespan—precluding the confirmation of these loci as coordinate modulators of adiposity and longevity. Our data also provide evidence for two QTLs previously shown to affect fuel efficiency under DR. In summary, the data do not support an important role for fat reduction in life extension by DR. They suggest instead that factors associated with maintaining adiposity are important for survival and life extension under DR.
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