10 replies to this topic

[Fafner55]

The attached list expands on Mitteldorf's and others’ lists of supplements that affect the lifespan of mice.

1. https://joshmitteldo...-trials-part-i/
2. https://joshmitteldo...ifespan-trials/
3. https://www.cell.com...8674(16)30981-3

 

Little evidence supports the idea that lifespans can be increased significantly through supplementation, as summarized in the attachment. 

 

The absence of demonstrated lifespan extension after decades of study of supplements and drugs is prima facie evidence that attempts to increase lifespan by modulating pro-aging biological pathways will show only marginal results. More significant benefits come instead from calorie restriction, senescent cell clearance, and promoting stem cell health and pool replenishment, mitophagy and autophagy, i.e., “house cleaning” and repair at a cellular and organismal levels.

 

 Lifespan Increase in Rodents From Various Interventions_2018-10_a.pdf   70.89KB   42 downloads

[SB_UK]

Excellent post - my personal favourite seen thus far.

 

Let me emphasize:

Little evidence supports the idea that lifespans can be increased significantly through supplementation.

 

So how do we do it ?

 

More significant benefits come instead from calorie restriction, senescent cell clearance, and promoting stem cell health and pool replenishment, mitophagy and autophagy, i.e., “house cleaning” and repair at a cellular and organismal levels.

 

 

See my intro thread - the realization that there are 2 states (2 overarching gene networks) and it's not therapeutic but lifestyle which is required to enter the longevity-promoting (disease preventative) network.

https://www.longecit...rch-powerpoint/

Edited by SB_UK, 12 October 2018 - 11:20 AM.

[MikeDC]

The 5% for NR is for 20-23 month old mice.  Supplementing NR earlier in life will most likely expand the benefits significantly.  

NR increased both average lifespan and maximum lifespan. Most supplements only expand average lifespan.

[Fafner55]

The 5% for NR is for 20-23 month old mice.  Supplementing NR earlier in life will most likely expand the benefits significantly.  

NR increased both average lifespan and maximum lifespan. Most supplements only expand average lifespan.

 

The mechanism of NR action is repletion of the age-related decline in NAD+. Supplementing NR earlier in life should have little if any effect on healthy individuals or mice.

 

The 5% increase in medium lifespan of mice with NR is backed by good science and should be accepted at face value. However, the combination of NR with other supplements, such as a bioavailable form of resveratrol could increase lifespan further since the effects of resveratrol decline in late passage cells, presumably due to insufficient NAD+. 

“Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation” (2015) https://www.scienced...30721X?via=ihub

 

This topic is addressed in another thread.

"Old human cells rejuvenated in breakthrough discovery on ageing" http://www.longecity...very-on-ageing/

[MikeDC]

The mechanism of NR action is repletion of the age-related decline in NAD+. Supplementing NR earlier in life should have little if any effect on healthy individuals or mice.

The 5% increase in medium lifespan of mice with NR is backed by good science and should be accepted at face value. However, the combination of NR with other supplements, such as a bioavailable form of resveratrol could increase lifespan further since the effects of resveratrol decline in late passage cells, presumably due to insufficient NAD+.
“Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation” (2015) https://www.scienced...30721X?via=ihub

This topic is addressed in another thread.
"Old human cells rejuvenated in breakthrough discovery on ageing" http://www.longecity...very-on-ageing/

NAD+ supplementation has value even for some people in their 30’s. Generally it is beneficial for people over 40. 20-23 month mice corresponds to 70 year old.

[Fafner55]

This list of lifespan extensions from various supplements and treatments is revised to include the senolytic fisetin and to highlight the benefits of autophagy.

 

 Lifespan Increase in Rodents From Various Interventions_2018-11-28.pdf   72.48KB   27 downloads

[Fafner55]

This list of the effects of various treatments on the lifespan of mice and rats is significantly expanded to include more treatments and reported changes in maximum lifespan. My previous lists only reported medium lifespan.

 

Interesting, but perhaps not surprising, is the larger maximum vs. medium lifespan extension of nicotinamide riboside (5% vs 12% Ref). This observation begs the question of what other cofactors besides NAD+ might decline exponentially with age, and correlate with and are predictive of mortality.

 

A surprising outcome of this study is olive oil. Notwithstanding extensive promotion and widespread adoptance, no life extension is reported from olive oil for any model organism. 

 

 Lifespan Increase in Mice From Various Interventions_2019-01-23.pdf   186.3KB   21 downloads

 

Edited by Fafner55, 23 January 2019 - 05:06 PM.

[Kimer Med]

 

My previous lists only reported medium lifespan.

 

What is "medium lifespan"? Or do you mean "median lifespan"?

[Fafner55]

What is "medium lifespan"? Or do you mean "median lifespan"?

 

Yes, I meant median lifespan. Typo. Corrected PDF is attached.

/Fafner55

 

 Lifespan Increase in Mice From Various Interventions_2019-01-23a.pdf   186.29KB   13 downloads

Edited by Fafner55, 23 January 2019 - 09:59 PM.

[Kimer Med]

Very interesting lists. Thanks for putting these together!

 

I suppose the logical next step is to synthesize a list of therapies that at least have the potential of being effective in humans, and to filter/refine that list based on studies done with primates or humans (if any): things we might try or at least consider for ourselves.

 

It may also be worth noting that the C60oo study in mice (the most effective therapy listed) couldn't be replicated, in spite of efforts to do so -- at least that's my understanding.

 

[Iporuru]

 

It may also be worth noting that the C60oo study in mice (the most effective therapy listed) couldn't be replicated, in spite of efforts to do so -- at least that's my understanding.

 

Are you aware of any such formal efforts? Can you provide links?