Fabrizio Paola, Battistella Luisa, Vardavas Raffaello, Gattazzo Cristina, Liou Lee-Loung, Diaspro Alberto, Dossen Janis W, Gralla Edith Butler, Longo Valter D
Andrus Gerontology Center and Dept. of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
J Cell Biol. 2004 Sep 27;166(7):1055-67. doi: 10.1083/jcb.200404002.
Aging is believed to be a nonadaptive process that escapes the force of natural selection. Here, we challenge this dogma by showing that yeast laboratory strains and strains isolated from grapes undergo an age- and pH-dependent death with features of mammalian programmed cell death (apoptosis). After 90-99% of the population dies, a small mutant subpopulation uses the nutrients released by dead cells to grow. This adaptive regrowth is inversely correlated with protection against superoxide toxicity and life span and is associated with elevated age-dependent release of nutrients and increased mutation frequency. Computational simulations confirm that premature aging together with a relatively high mutation frequency can result in a major advantage in adaptation to changing environments. These results suggest that under conditions that model natural environments, yeast organisms undergo an altruistic and premature aging and death program, mediated in part by superoxide. The role of similar pathways in the regulation of longevity in organisms ranging from yeast to mice raises the possibility that mammals may also undergo programmed aging.
衰老被认为是一个逃避自然选择力量的非适应性过程。在此,我们通过证明酵母实验室菌株和从葡萄中分离出的菌株会经历与年龄和pH值相关的死亡,并具有哺乳动物程序性细胞死亡(凋亡)的特征,来挑战这一教条。在90%-99%的群体死亡后,一个小的突变亚群利用死细胞释放的营养物质生长。这种适应性再生长与对超氧化物毒性的抗性和寿命呈负相关,并且与年龄依赖性营养物质释放增加和突变频率增加有关。计算模拟证实,早衰以及相对较高的突变频率可导致在适应不断变化的环境中具有重大优势。这些结果表明,在模拟自然环境的条件下,酵母生物体经历了一种利他性的早衰和死亡程序,部分由超氧化物介导。类似途径在从酵母到小鼠等生物体的寿命调节中的作用增加了哺乳动物也可能经历程序性衰老的可能性。