Department of Biosciences and Medical Biology, Paris-Lodron University Salzburg, 5020 Salzburg, Austria.
Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
Biomolecules. 2023 May 30;13(6):912. doi: 10.3390/biom13060912.
It is widely accepted that nine hallmarks-including mitochondrial dysfunction, epigenetic alterations, and loss of proteostasis-exist that describe the cellular aging process. Adding to this, a well-described cell organelle in the metabolic context, namely, lipid droplets, also accumulates with increasing age, which can be regarded as a further aging-associated process. Independently of their essential role as fat stores, lipid droplets are also able to control cell integrity by mitigating lipotoxic and proteotoxic insults. As we will show in this review, numerous longevity interventions (such as mTOR inhibition) also lead to strong accumulation of lipid droplets in , , , and mammalian cells, just to name a few examples. In mammals, due to the variety of different cell types and tissues, the role of lipid droplets during the aging process is much more complex. Using selected diseases associated with aging, such as Alzheimer's disease, Parkinson's disease, type II diabetes, and cardiovascular disease, we show that lipid droplets are "Janus"-faced. In an early phase of the disease, lipid droplets mitigate the toxicity of lipid peroxidation and protein aggregates, but in a later phase of the disease, a strong accumulation of lipid droplets can cause problems for cells and tissues.
人们普遍认为，有九个标志描述了细胞衰老过程，包括线粒体功能障碍、表观遗传改变和蛋白质稳态丧失。此外，在代谢背景下，一种被充分描述的细胞细胞器——脂滴，也随着年龄的增长而积累，这可以被视为另一个与衰老相关的过程。脂滴不仅作为脂肪储存的基本功能，还能够通过减轻脂毒性和毒性蛋白的损伤来控制细胞完整性。正如我们将在这篇综述中展示的，许多长寿干预措施（如 mTOR 抑制）也会导致脂质滴在酵母、秀丽隐杆线虫、果蝇和哺乳动物细胞中大量积累，仅举几个例子。在哺乳动物中，由于存在多种不同的细胞类型和组织，因此脂滴在衰老过程中的作用要复杂得多。我们使用与衰老相关的一些疾病（如阿尔茨海默病、帕金森病、二型糖尿病和心血管疾病）来证明脂滴具有“两面性”。在疾病的早期阶段，脂滴减轻脂质过氧化和蛋白质聚集体的毒性，但在疾病的后期阶段，脂滴的大量积累会给细胞和组织带来问题。
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