衰老是由满足以下三个前提的标志驱动的:(1)与年龄相关的表现,(2)通过实验强调它们而加速衰老,以及(3)通过治疗干预来减缓、停止或逆转衰老的机会他们。我们提出了以下十二个衰老标志:基因组不稳定、端粒磨损、表观遗传改变、蛋白质稳态丧失、巨自噬功能障碍、营养感应失调、线粒体功能障碍、细胞衰老、干细胞耗竭、细胞间通讯改变、慢性炎症和生态失调。这些特征相互关联,也与最近提出的健康特征相互关联,其中包括空间划分的组织特征、体内平衡的维持以及对压力的充分反应。

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As I see it apart from stem cell exhaustion the main cause is the failure of long genes to function in sufficient number. Stem cell exhaustion is probably linked to HIF 1 alpha and the lack of exercise (use it or lose it territory).

As a Hallmark I would add alternate RNA splicings, however.

Further there is a video on this:

Additionally:

Proposes 5 new hallmarks of aging including

"Dysregulation of RNA processing has been noted in human ageing population studies [13] while interventions thatappear to reverse senescent phenotypes act at least in part by restoring youthful patterns of splicing factor expression [14].

Similarly, alternative polyadenylation of mRNAs, already known to contribute to cancer [15] is altered with ageing and may contribute to senescence [16]. Such changes in RNA processing add an additional layer of gene expression control over those of genome integrity, transcriptional efficacy and epigenetic regulation that are already known to change during biological ageing."

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Are there any known interventions to prevent stem cell exhaustion?

I think you can increase stem cell populations through HIF 1 alpha. I intend to do some experiments on this probably later this month. I am trying to get a baseline reticulocyte count that I can rely on then try to increase it.

Exercise is a good way of stimulating HIF 1 alpha.

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Has anyone noticed that the three new hallmarks of aging seem to all be directly addressed by taking Rapamycin? It seems like they were written just for Rapa!


• Chronic inflammation - A long-term immune response that can damage tissue and lead to age-related diseases.

• Disabled macroautophagy - A disruption in cellular self-cleaning (autophagy) that leads to a buildup of waste and is associated with metabolic disorders and cancer.

• Dysbiosis - An imbalance in the gut microbiome that can increase the risk of inflammation, infection, and chronic disease.

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