Spermidine-Induced Autophagy: Unlocking the Secrets to Geroprotection

亚精胺诱导的自噬:揭开老年保护的秘密

介绍

衰老是生命中不可避免的一部分,随着年龄的增长,我们的身体会发生各种变化。其中一种变化是细胞功能的逐渐衰退,导致罹患与年龄相关的疾病的风险更高。科学家们一直在研究促进健康衰老和延长寿命的方法,最近的研究强调了一种名为亚精胺的分子在这一过程中的潜力。

《自然衰老》杂志发表的一项题为《 亚精胺诱导自噬和抗衰老机制》的研究揭示了亚精胺对自噬和衰老影响的细胞机制。本文将深入研究该研究结果,并讨论其对人类健康和长寿的影响。

亚精胺:天然的老年保护剂

亚精胺是一种天然存在的多胺,存在于多种食物中,例如大豆、豆类、蘑菇和陈年奶酪。研究表明,亚精胺具有许多健康益处,包括促进自噬,这是一种负责分解和回收受损细胞成分的细胞过程。

自噬对于维持细胞健康和功能至关重要,其随着年龄的增长而下降,与年龄相关疾病的风险增加有关。亚精胺刺激自噬的能力使其成为老年保护的有前途的候选者,老年保护是指促进健康衰老和预防与年龄相关的疾病的干预措施。

 

自噬与衰老
自噬是一种高度保守的细胞过程,在维持细胞稳态中发挥着至关重要的作用。它通过去除受损的细胞器、错误折叠的蛋白质和入侵的病原体来发挥质量控制机制的作用。自噬随着年龄的增长而下降,导致受损细胞成分的积累,并导致衰老和与年龄相关的疾病。


亚精胺已被证明可以诱导自噬,这是它被认为是衰老保护剂的原因之一。通过促进自噬,亚精胺可能有助于抵消衰老的负面影响并改善整体健康。


亚精胺诱导自噬的机制
Madeo 等人的研究全面概述了亚精胺诱导自噬的分子机制。作者描述了亚精胺发挥其自噬诱导作用的几种途径:


1.抑制乙酰转移酶:亚精胺抑制一组称为乙酰转移酶的酶,从而导致自噬的激活。这种作用主要归因于对EP300的抑制,EP300是一种参与自噬调节的特定乙酰转移酶。


2.激活脱乙酰酶:亚精胺还会激活一组称为脱乙酰酶的酶,特别是 sirtuin 1 (SIRT1),已知它可以促进自噬。 SIRT1 激活增强自噬相关蛋白的脱乙酰化,导致自噬激活。


3.转录因子的调节:亚精胺调节多种转录因子,例如转录因子EB (TFEB)叉头盒O3 (FOXO3)蛋白,它们调节表达自噬相关基因。


4.诱导线粒体功能和生物发生:亚精胺促进线粒体功能生物发生,这对于维持细胞能量稳态和防止受损线粒体的积累至关重要。导致衰老的因素。


5.细胞应激反应的调节:亚精胺参与多种应激反应的调节,包括未折叠蛋白反应 (UPR)、热休克反应氧化应激反应。通过调节这些应激反应,亚精胺增强细胞弹性并促进自噬。

《自然衰老》杂志上的这项研究旨在揭示亚精胺对自噬和抗衰老作用背后的细胞机制。研究人员结合了遗传、生物化学和细胞方法来研究亚精胺如何调节自噬并促进健康衰老。

他们发现亚精胺的衰老保护作用主要是通过激活一种名为 EP300 的蛋白质来介导的,EP300 是自噬的重要调节因子。 EP300 激活一种名为 TFEB 的转录因子,进而促进参与自噬和溶酶体功能的基因的表达。

研究还发现,亚精胺诱导的 EP300 激活依赖于其结合和抑制另一种名为 SIRT1 的蛋白质的能力,SIRT1 是一种众所周知的衰老和寿命调节因子。亚精胺对 SIRT1 的抑制会导致 EP300 活性增加,从而增强自噬和细胞健康。

值得注意的是,研究人员证明,在缺乏 EP300 或 SIRT1 的细胞中,亚精胺的老年保护作用显着降低,凸显了这些蛋白质在亚精胺作用中的重要性。

对人类健康和长寿的影响

这项研究的结果对人类健康和寿命有几个重要的影响。通过揭示亚精胺诱导的自噬和衰老保护的分子机制,该研究为促进健康衰老和预防与年龄相关的疾病的潜在策略提供了宝贵的见解。

首先,该研究强调了自噬及其通过EP300和SIRT1的调节在维持细胞健康中的重要性。更好地了解这些过程可能会导致开发新的治疗干预措施,以增强自噬并改善老龄化人群的健康结果。

其次,该研究强调了补充亚精胺对于促进健康衰老的潜在益处。由于亚精胺是一种天然存在于各种食物中的化合物,因此增加其饮食摄入量可能是利用其老年保护作用的实用且非侵入性的方法。需要在人体中进行进一步的临床试验,以确定补充亚精胺用于老年保护的最佳剂量、安全性和功效。

最后,该研究为衰老和老年保护领域的研究开辟了新途径。研究亚精胺、EP300 和 SIRT1 之间的相互作用以及它们在自噬和细胞健康中的作用,可以揭示促进长寿和健康衰老的干预措施的其他目标。通过阐明 EP300 和 SIRT1 在亚精胺诱导的自噬中的作用,这项研究为未来针对这些蛋白质及其相关途径的研究和潜在治疗干预铺平了道路。

 

Mechanisms of spermidine-induced autophagy and geroprotection

结论
随着全球人口持续老龄化,制定有效策略来促进健康老龄化和预防与年龄相关的疾病变得越来越重要。亚精胺增强自噬和促进老年保护的能力为应对这一挑战提供了一条有希望的途径。

虽然还需要进行更多的研究来充分了解亚精胺、EP300 和 SIRT1 的复杂相互作用,并确定在人体中补充亚精胺的最佳方法,但这项研究是我们追求更健康、更长寿的关键垫脚石。全部。


随着我们对控制细胞健康和衰老的复杂过程的了解不断加深,改善人类健康和延长寿命的创新、有效策略的潜力变得越来越明显。将富含亚精胺的食物纳入我们的饮食中或考虑补充亚精胺(有待进一步研究和临床试验)可能被证明是我们追求更长寿、更健康生活的宝贵工具。

最终,这项研究的结果不仅强调了自噬在维持细胞健康和衰老方面的重要性,而且还强调了亚精胺作为衰老保护剂的潜力。通过靶向参与自噬和细胞健康的关键蛋白质和途径,亚精胺为延长寿命和减轻与年龄相关的疾病负担提供了一种有前景的方法。

随着科学家们不断探索饮食、细胞过程和衰老之间的复杂关系,越来越清楚的是,对这些联系的更深入了解可能会对人类健康和福祉产生深远影响。对亚精胺、EP300 和 SIRT1 的研究证明了该领域突破性发现的潜力,为改善老年人群的健康状况和提高生活质量铺平了道路。

通过将从此类研究中获得的知识融入到我们的日常生活中,我们可以对支持健康老龄化的饮食和生活方式做出明智的选择。从长远来看,这些微小的变化可能共同为个人和社区带来更光明、更健康的未来。

 

参考:

 

1. Hofer, S.J.、Simon, A.K.、Bergmann, M. 等人。亚精胺诱导的自噬和衰老保护机制。自然老龄化 2, 1112–1129 (2022)。 https://doi.org/10.1038/s43587-022-00322-9。

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