Compelling evidence suggests that lipid metabolism, which plays critical roles in fat storage, cell membrane maintenance, and cell signaling, is intricately linked to aging. Lipid hydrolases are important enzymes that catalyze the hydrolysis of more complex lipids into simpler lipids. Diverse interventions targeting lipid hydrolases can prolong or shorten life in model organisms. For example, the genetic removal of or RNAi knockdown against a phospholipase can reduce lifespan in Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. The removal of lysosomal acid lipase results in premature death in mice, while its overexpression in nematodes generates lean, long-lived individuals. The overexpression or inhibition of diacylglycerol lipase leads to enhanced or reduced longevity, respectively, in both worms and flies. Lifespan can also be extended by knocking down triacylglycerol lipases in yeast, overexpressing fatty acid amide hydrolase in worms, or removing hepatic lipase in a mouse model of coronary disease. Conversely, flies lacking the triacylglycerol lipase Brummer are obese and short lived. Linking sphingolipids and aging, removing the sphingomyelinase inositol phosphosphingolipid phospholipase shortens chronological lifespan in Saccharomyces cerevisiae, while inhibiting an acid sphingomyelinase in worms or inactivating alkaline ceramidase in flies extends lifespan. The clinical potential of manipulating these enzymes is highlighted by the FDA-approved obesity drug orlistat, which is an inhibitor of pancreatic and hepatic lipases that induces weight loss and improves insulin/glucose homeostasis. Additional research is warranted to better understand how these lipid hydrolases impact aging and to determine if clinical interventions targeting them are capable of improving human healthspan.

中文翻译：

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脂质水解酶：延长人类健康的实用寿命指标？

有力的证据表明，脂质代谢在衰老过程中起着至关重要的作用，而脂质代谢在脂肪储存，细胞膜维持和细胞信号传导中起着至关重要的作用。脂质水解酶是重要的酶，可催化更复杂的脂质水解为更简单的脂质。针对脂质水解酶的多种干预措施可以延长或缩短模型生物的寿命。例如，遗传去除磷脂酶或RNAi敲低磷脂酶可减少秀丽隐杆线虫，果蝇和小家鼠的寿命。。溶酶体酸性脂肪酶的去除导致小鼠过早死亡，而其在线虫中的过表达则产生了瘦长寿的个体。二酰基甘油脂肪酶的过度表达或抑制分别导致蠕虫和果蝇的寿命延长或减少。还可以通过敲低酵母中的三酰基甘油脂肪酶，在蠕虫中过表达脂肪酸酰胺水解酶或在冠心病的小鼠模型中去除肝脂肪酶来延长寿命。相反，缺乏三酰基甘油脂肪酶Brummer的果蝇肥胖且寿命短。将鞘脂与衰老联系起来，去除鞘磷脂酶肌醇磷酸鞘脂磷脂酶可缩短酿酒酵母的时间寿命，而在蠕虫中抑制酸性鞘磷脂酶或使苍蝇中的碱性神经酰胺酶失活可延长寿命。FDA批准的肥胖药orlistat强调了操纵这些酶的临床潜力，该药是胰腺和肝脂肪酶的抑制剂，可诱导体重减轻并改善胰岛素/葡萄糖体内稳态。有必要进行额外的研究，以更好地了解这些脂质水解酶如何影响衰老，并确定针对它们的临床干预措施是否能够改善人类健康。