Hallmarks of Aging 2.0

Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organizational features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.

Full paper:


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:


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."


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.