4 replies to this topic

[reason]

Enhancing levels of NAD+ in mitochondria via delivery of various precursor compounds as supplements is growing in popularity as an approach to boost faltering mitochondrial function and thus modestly slow the progression of aging. A human trial demonstrated improved vascular function as a result of nicotinamide riboside supplementation, for example. Researchers here show that increased NAD+ will likely make worse the inflammatory signaling of senescent cells, however. Senescent cells accumulate with age, and are an important cause of the chronic inflammation of aging that drives the progression of many age-related diseases.

The results here suggest that efficient senolytic treatments to selectively destroy senescent cells should proceed any of the current approaches to raising levels of NAD+ in older individuals - and it is an open question as to whether any of the existing available options are efficient enough to make NAD+ enhancement safe in the longer term. Those people self-experimenting with NAD+ precursor supplementation should consider keeping a close eye on markers of inflammation.

Cellular senescence is a stable growth arrest that is implicated in tissue ageing and cancer. Senescent cells are characterized by an upregulation of proinflammatory cytokines, which is termed the senescence-associated secretory phenotype (SASP). NAD+ metabolism influences both tissue ageing and cancer. However, the role of NAD+ metabolism in regulating the SASP is poorly understood. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway, governs the proinflammatory SASP independent of senescence-associated growth arrest.

NAMPT expression is regulated by high mobility group A (HMGA) proteins during senescence. The HMGA-NAMPT-NAD+ signalling axis promotes the proinflammatory SASP by enhancing glycolysis and mitochondrial respiration. HMGA proteins and NAMPT promote the proinflammatory SASP through NAD+-mediated suppression of AMPK kinase, which suppresses the p53-mediated inhibition of p38 MAPK to enhance NF-κB activity. We conclude that NAD+ metabolism governs the proinflammatory SASP. Given the tumour-promoting effects of the proinflammatory SASP, our results suggest that anti-ageing dietary NAD+ augmentation should be administered with precision.

Link: https://doi.org/10.1...1556-019-0287-4

View the full article at FightAging

[Engadin]

Good find reason.

 

Here the whole text (.pdf).

 

In this study, the most mentioned 'Nad+ -augmenting dietary supplement' is nicotinamide mononucleotide NMN. AFAIK direct bloodflow supplementation by sublingual NAD+ is not cited. However this last one might get involved in increasing NAD+/NADH ratio and therefore in 'high SASP-associated  senescence  such  as  OIS  predominantly  driven  by  a high  NAD+/NADH  ratio,  ... '. So, is your opinion that sublingual NAD+ should be included in this serious warning?.

 

 

 

Edited by Engadin, 06 May 2019 - 12:21 PM.

[Engadin]

Too late to edit my last post and the bad link to the whole text.

 

Please find it here.

 

In addition, let me put my thoughts this way:

 

In the coloured graph at the end of the above mentioned .pdf labeled with letter 'h', (I am unable to bring it here nor in .jpg or .png format)  it looks like direct bloodflow sublingual NAD+ supplementation would seen to bypass the HMGA-mediated NAMPT expression and therefore oncogene induced senescence (OIS) and then the high inflammatory SASP accompanying it and also the one generated by NAD+ metabolism. It then would look like sublingual NAD+ producing only a low grade imflammatory SASP. 

Edited by Engadin, 06 May 2019 - 01:20 PM.

[Mind]

I see this as similar to the oft-cited theme about cancer. Almost any treatment you take that boosts the activity/energy/fidelity of regular cells, will tend to do the same for cancer cells. Perhaps it is similar for senescent cells.

 

The key would be do the benefits outweigh the risk.

 

Anyone know (or can share a graph) showing the increase in SASP wwith NAD+ boosting supplementation?

[ledgf]

>Almost any treatment you take that boosts the activity/energy/fidelity of regular cells, will tend to do the same for cancer cells. 

Quite the opposite. Anything that improves mitochondrial health will tend to activate apoptosis in cancer cells, while helping or being neutral in normal cells. We've known this since Warburg in 1935.