Interactions between mitochondrial dysfunction and other hallmarks of aging: Paving a path toward interventions that promote healthy old age

This is interesting. Mitochondrial disfunction <—> Hallmarks of Aging

Interactions between mitochondrial dysfunction and other hallmarks of aging: Paving a path toward interventions that promote healthy old age

Current research on human aging has largely been guided by the milestone paper “hallmarks of aging,” which were first proposed in the seminal 2013 paper by Lopez- Otin et al. Most studies have focused on one aging hallmark at a time, asking whether the underlying molecular perturbations are sufficient to drive the aging process and its associated phenotypes. More recently, researchers have begun to investigate whether aging phenotypes are driven by concurrent perturbations in molecular pathways linked to not one but to multiple hallmarks of aging and whether they present different patterns in organs and systems over time. Indeed, preliminary results suggest that more complex interactions between aging hallmarks must be considered and addressed, if we are to develop interventions that successfully pro-mote healthy aging and/or delay aging- associated dysfunction and diseases. Here, we summarize some of the latest work and views on the interplay between hall -marks of aging, with a specific focus on mitochondrial dysfunction. Indeed, this rep-resents a significant example of the complex crosstalk between hallmarks of aging and of the effects that an intervention targeted to a specific hallmark may have on the others. A better knowledge of these interconnections, of their cause- effect relationships, of their spatial and temporal sequence, will be very beneficial for the whole aging research field and for the identification of effective interventions in promoting healthy old age

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From the paper:
“Chronic treatment of humans with high doses of rapalogs is associated with deleterious metabolic consequences including hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, insulin resistance, and glucose intolerance, which seem to be reduced by intermittent or low-dose regimens of the drugs (Mannick & Lamming, 2023)”

I started rapamycin with high doses based on studies and statements at the time that more was better, especially if you were old.
Rapamycin at high doses screwed up virtually all of my blood work. I have continually reduced the rapamycin dose protocol and now everything is fine. Currently, I am doing 1mg daily one week on and one week off.


It is an interesting collection of information. However, i think science has in some ways moved on from this.

What seems clear to me is that bad quality mitochondria are a partial cause of the phenotypes of aging.

Apart from the acetyl coa issue there is clearly a problem for cells when there is not enough ATP to produce all the proteins that cells need.

This also seems to skew failure in some way towards particular proteins and at the translation stage stalled translations probably are sent to ribosome quality control.

Obviously damaged mitochondria can be recycled which is where Rapamycin helps. However, there are also tools for increasing ATP availability.

I have now got a big box of ATP promoting supplements and intend experimenting with combining their effects in September.

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Nick Lane from the University College London is one of the leaders in mitochondria research.

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