NMN and Resveratrol
Feb 01, 2021

David recently garnered attention with his appearances on the Rhonda Patrick and Joe Rogan podcasts. Using his moment in the spotlight to raise awareness for life extension research.

Despite being 50 years of age, David looks much younger. Given that his focus is on tackling aging and he appears to exemplify this work – it’s natural to ask – what’s his secret?

One thing David is fast to point out is that he’s a scientist – not a medical doctor, and doesn’t give health recommendations. Respecting that, this post will only look at what David does, noting that he isn’t recommending others do the same. David does not sell or endorse any brands – so the discussion below on “where to buy” will simply look at options.

NMN and Resveratrol

David Sinclair Takes:

Resveratrol – 1g/daily – mornings with yogurt (see where to buy)

Nicotinamide Mononucleotide (NMN) – 1g/daily – mornings (see where to buy)

Metformin (prescription drug) – 1g/daily – 0.5g in the morning & 0.5g at night – except on days when exercising

Vitamins? Aims to get majority from diet, but does supplement a few including vitamin D & K2 – see this section

Statin (prescription drug) – taken since his early 20s due to family history of cardiovascular disease

Aspirin – 83mg daily

For a complete list of sources for the above, see this section.

Transcriptome analysis of preparations enriched for cells of the neurovascular unit was performed by RNA-seq. Neurovascular gene expression signatures in NMN-treated aged mice were compared with those in untreated young and aged control mice. We identified 590 genes differentially expressed in the aged neurovascular unit, 204 of which are restored toward youthful expression levels by NMN treatment.

The transcriptional footprint of NMN treatment indicates that increased NAD+ levels promote SIRT1 activation in the neurovascular unit, as demonstrated by analysis of upstream regulators of differentially expressed genes as well as analysis of the expression of known SIRT1-dependent genes. Pathway analysis predicts that neurovascular protective effects of NMN are mediated by the induction of genes involved in mitochondrial rejuvenation, anti-inflammatory, and anti-apoptotic pathways.

In conclusion, the recently demonstrated protective effects of NMN treatment on neurovascular function can be attributed to multifaceted sirtuin-mediated anti-aging changes in the neurovascular transcriptome. Our present findings taken together with the results of recent studies using mitochondria-targeted interventions suggest that mitochondrial rejuvenation is a critical mechanism to restore neurovascular health and improve cerebral blood flow in aging.

resveratrol and nmn

What do Resveratrol & NMN do in relation to living longer?

David describes resveratrol and NMN as critical for the activation of sirtuin genes. Sirtuins play a key role in functions that help us to live longer – such as DNA repair.

He describes resveratrol as the “accelerator pedal” for the sirtuin genes (increasing their activation), and NMN as the fuel. Without “fuel”, resveratrol won’t work. The reason that resveratrol won’t work effectively without NMN, is that sirtuin activation requires youthful NAD levels, but by 50 years old, we have about half the level of NAD we had in our 20s (NAD being a molecule that is essential to energy production in our cells).

So in effect, you take resveratrol to increase activation of the sirtuin genes, and NMN to ensure the sirtuins have enough energy to work properly.

What else is David doing to stay healthy?

Intermittent fasting – skipping breakfast and/or lunch where possible. Helped by lots of green tea

Running 1-2x/week low impact and high intensity (using a curved treadmill such as Woodway)

Weight lifting (ideally!) 1-2x/week

Sauna weekly

Coffee in the morning (once per day), then green tea after that

Below we’ll dig deeper into the 3 longevity supplements David takes; NMN, Resveratrol & Metformin.

nmn and resveratrol before and after

NMN and Resveratrol before and after

At the most fundamental level, at the very least, one should statistically compare the before & after measurements of our proxy measurements. An added benefit would be the inclusion of additional baseline measurements from before the experiment begins. This inherently needs to include some basic corrections for the non-stationary nature of the data. In layperson terms - chronological time is passing over our measurement period. So the ‘after’ measurements should be corrected in our analysis, considering the amount of time that has passed over the course of the experiment.

Lastly, and perhaps more importantly, we must employ purposeful management of potential confirmation bias. Anyone who is running an NMN self-experiment and is looking after their longevity wants and likely expects the supplement to work. Since we know the result we want, therefore we need to be defensive against our bias when we draw conclusions based on this result. This is particularly relevant for bloggers and social media focussed folks - we inherently want the Ben Greenfield headline to draw clicks and eyeballs.

I refuse to do that to you, and will revisit these issues when we analyse the data and draw our conclusions.

For bulk NMN, bulk Resveratrol, contact us at email: [email protected]


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