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衰老主要指生物体在成年后的功能衰退。从2013年cell杂志发表的第一篇《衰老的标志》算起，距今已有近30万篇与之主题相关的文章。总结起来与衰老相关的标准有12个，本文详细阐述了这12个衰老特征，全方位的了解衰老才能使我们更好的减缓阻止或逆转衰老。

Aging mainly refers to the functional decline of an organism in adulthood. From the first ‘Signs of Aging’ published by cell magazine in 2013, there have been nearly 300,000 articles related to this topic, summarizing 12 criteria related to aging. This article elaborates on these 12 characteristics of aging, a comprehensive understanding of aging can make us better slow down to stop or reverse aging.

The following three criteria need to be met 

to be assessed as a characteristic of aging

1. time-dependent.

2. acceleration of aging by experimental interventions.

3. therapeutic interventions on the hallmarks of aging can slow, stop, or reverse aging.

基因组的不稳定性

Genomic instability

端粒损耗

Telomere attrition

表观遗传学改变

Epigenetic alterations

Epigenetic alterations affect gene expression and other cellular physiological processes such as cancer, neuropathy, metabolic syndrome, and other degenerative diseases. This regulation is often reversible.

[DNA Methylation] DNA methylation undergoes a variety of adverse changes during aging. For example, some tumor suppressor genes become hypermethylated with age. Cells from patients with premature aging syndrome also show changes in DNA methylation compared to healthy people. In short, DNA methylation is associated with aging, but there is no conclusive evidence that it causes aging.[histone modification] The total absence of histones and their post-translational modification changes are also strongly associated with aging. Increased histone expression extends lifespan in Drosophila, but in fibroblasts of the elderly, histone H4K16 acetylation and H3K4 trimethylation are increased, and the levels of H 3 K 9 and H3K27 trimethylation are decreased, and these changes lead to transcriptional changes, imbalance in cellular state, and decreased metabolism.[Chromosome remodeling] Some chromosomal proteins and chromosome repair factors, such as heterochromatin protein 1 alpha (HP1α) and polyribosomal histones (which are associated with genome-stabilizing DNA repair) are also involved in the regulation of senescence[Non-coding RNAs] Non-coding RNAs include INC RNAs, (e.g. telomeric RNAs or TERRA) MICRO RNAs and cyclic RNAs. as an example, upregulation of miR-188-3P affects vascular status.[Depressorization of retrotransposons] These reversible transposons are mobile genetic units that can move from one genomic location to another. Reactivation of retrotransposons can produce adverse effects on longevity through genetic and epigenetic changes. The longevity gene SIRT6 inhibits this effect.

[ Gene Expression Changes ] The mechanisms of action of all of the above epigenetic factors are related to the regulation of gene expression levels. Aging leads to increased transcription errors and abnormalities in mRNA ripening. These transcriptional changes observed during aging and the negative effects on the proteome could open new possibilities for life extension strategies.

蛋白稳态丧失

Loss of proteostasis 

巨自噬功能降低

Disabled macroautophagy

巨自噬是指

将细胞质物质封存在自噬体内

并与溶酶体结合进行消化

需要被自噬的物质包括而不限于

突变基因、错误的蛋白、老废的细胞器

病原体、失活的核糖体

可见自噬功能与蛋白质稳态

非蛋白质大分子和整个细胞器功能调节

入侵的病原体清除能力及炎症反应有关

更有研究指出

自噬受到短暂抑制后

恶性肿瘤的发病率大幅上升

随着年龄增长自噬功能下降

会导致细胞器周转率降低

因此自噬功能被视为衰老的新标志

在分子层面

人们发现自噬相关基因的表达量

会随着年龄增长而下降

细胞自噬通量也因此受到影响

与之相应的是长寿人群后代中

分离出的ct4  T淋巴细胞

能显示出更强的自噬活性

Macroautophagy refers to the sequestration of cytoplasmic material within the autophagosome and binding to lysosomes for digestion, and the material to be autophagized includes, but is not limited to, mutanted genes, inaccurate translation, dysfunctional organelles, pathogens, and inactivated ribosomes. It is evident that autophagy function is related to protein homeostasis, regulation of non-protein macromolecules and whole organelle function, clearance of invading pathogens, and inflammatory response. It has even been noted that the incidence of malignant tumors increases dramatically after autophagy is transiently inhibited. Decreased autophagy with age leads to decreased organelle turnover. Therefore, autophagy is regarded as a marker of aging. At the molecular level, it has been found that the expression of autophagy-related genes decreases with age, and cellular autophagic flux is consequently impacted. Correspondingly, ct4 T lymphocytes isolated from the offspring of long-lived people can show stronger autophagic activity.

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