Longevity strategies in response to light in the reef coral Stylophora pistillata

Aging is a multifactorial process that results in progressive loss of regenerative capacity and tissue function while simultaneously favoring the development of a large array of age-related diseases. Evidence suggests that the accumulation of senescent cells in tissue promotes both normal and pathological aging. Oxic stress is a key driver of cellular senescence. Because symbiotic long-lived reef corals experience daily hyperoxic and hypoxic transitions, we hypothesized that these long-lived animals have developed specific longevity strategies in response to light. We analyzed transcriptome variation in the reef coral Stylophora pistillata during the day–night cycle and revealed a signature of the FoxO longevity pathway. We confirmed this pathway by immunofluorescence using antibodies against coral FoxO to demonstrate its nuclear translocation. Among genes that were specifically up- or downregulated on exposure to light, human orthologs of two “light-up” genes (HEY1 and LONF3) exhibited anti-senescence properties in primary human fibroblasts. Therefore, these genes are interesting candidates for counteracting skin aging. We propose a large screen for other light-up genes and an investigation of the biological response of reef corals to light (e.g., metabolic switching) to elucidate these processes and identify effective interventions for promoting healthy aging in humans. RNA-Seq of tissues of coral Stylophora pistillata was performed using SOLiD 3 sequencer in three biological replicates.

衰老是一种多因素参与的生理过程，会导致再生能力与组织功能进行性丧失，同时助推各类年龄相关性疾病的发生发展。已有研究表明，组织中衰老细胞（senescent cells）的积累会同时促进生理性衰老与病理性衰老。氧化应激是细胞衰老的关键驱动因素。由于共生性长寿造礁珊瑚每日都会经历高氧与低氧的周期性转换，本研究推测这类长寿动物已演化出应对光照的特异性长寿策略。本研究对昼夜周期中造礁珊瑚杯形珊瑚（Stylophora pistillata）的转录组（transcriptome）变化进行了分析，揭示了FoxO长寿通路的特征性信号。本研究通过使用针对珊瑚FoxO的抗体开展免疫荧光实验，验证了该通路的核转位现象。在光照暴露后特异性上调或下调的基因中，两个“光照响应基因（light-up genes）”的人类同源基因HEY1与LONF3，在人类原代成纤维细胞中表现出抗细胞衰老的特性。因此，这两个基因可作为对抗皮肤衰老的潜在候选靶点。本研究建议针对其他光照响应基因开展大规模筛选，并深入探究造礁珊瑚对光照的生物学应答（例如代谢重编程），以阐明上述过程，并筛选出可促进人类健康衰老的有效干预手段。本研究使用SOLiD 3测序仪对杯形珊瑚（Stylophora pistillata）的组织样本进行了RNA测序（RNA-Seq），共设置3次生物学重复。