Why NAD+ declines with age


We talk a lot about the importance of NAD+ and why it is so valuable to maintain your NAD+ levels as you age for maintaining your active and healthy lifestyle. But to truly appreciate how Nuchido TIME+ works and how this is different to other NAD+ supplements, we must understand what happens to our NAD+ levels as we age and why they decline, because just like everything in biology it is a complex topic.

 

Our NAD+ levels half every 20 years

Research has shown that our NAD+ levels decline by around 50% every 20 years, which is alarming as we know NAD+ is vital to maintaining cellular health. This is because NAD+ is a vital coenzyme and is involved in over 500 chemical reactions within our cells particularly those for energy production and activation of longevity genes (sirtuins).

So, what causes this progressive NAD+ decline as we age…?

 

NAD+ production declines with age

NAD+ is a large molecule meaning it cannot just be added into the cell, it has to be manufactured inside the cell from precursors (that is any substance which can be used to manufacture NAD+) this means we cannot just absorb NAD+ directly from the nutrients in our food.

Unfortunately, the NAD+ production pathways in the cell become less efficient as we get older.

In young cells NAD+ is synthesized via various pathways and when used up, the waste product called nicotinamide is recycled back into fresh NAD+ by the Salvage Pathway. This recycling process is the main source of NAD+ within our cells and is one of the main reasons NAD+ levels decline with age.

The enzyme which powers the salvage pathway is called NAMPT and it is this enzyme specifically which has been shown to decline with age and causes the NAD+ recycling capabilities of the cell also decline. That is why part of the Nuchido TIME+ formulation is dedicated to increasing levels of the NAMPT enzyme and enhancing the recycling capabilities of the cell.

 

NAD+ consumption increases with age

In addition to the decreased production of NAD+ there is also an increased demand for NAD+ within the cell. It is well known that NAD+ is used by many different proteins within the cell to power chemical reactions and some of these proteins are known to increase with age and therefore consume more NAD+. Two of the major NAD+ consumers are PARP enzymes and CD38.

PARP enzymes are involved in maintaining healthy DNA so ensuring they get enough NAD+ is vital. CD38 has been well studied and is now understood to the be the largest NAD+ consumer in mammalian cells, CD38 levels increase greatly in older cells meaning it wastes a huge amount of the already limited NAD+. Nuchido TIME+ contains ingredients which inhibit CD38 preventing it from wasting NAD+.  

The increased NAD+ consumption in turn generates more waste nicotinamide (NAM) and we know that older cells have decreased ability to recycle this nicotinamide back into fresh NAD+. The result is accumulation of NAM which has to be methylated and excreted from the cell leading to methyl donor depletion. Nuchido TIME+ also contains ingredients that inhibit this methylation process which in combination with enhancing the salvage pathway support recycling of NAM back into fresh NAD+.

 

Increased Demand and Decreased Supply

Collectively, this increased demand and decreased supply leaves the various cellular pathways fighting over a dwindling supply of NAD+ right at the time when they could do with more NAD+. As we can see NAD+ biology and its subsequent decline with age is a complex subject. NAD+ decline isn’t just a result of one thing therefore, any approach to enhance NAD+ levels needs to understand and appreciate this complexity.

NAD decline  

That is exactly what Nuchido TIME+ does. It is specially formulated to increase the activity of the salvage pathway allowing the cell to recycle and make NAD+, whilst also preventing the cell from wasting NAD+. 

We have completed a double-blinded, placebo-controlled crossover study on our next generation NAD+ boosting supplement, Nuchido TIME+. THe results demonstrated:

  • Nuchido TIME+ significantly increases cellular NAD+ after only 7 days
  • Unlike NR or NMN it works by switching back on youthful cellular NAD+ production by reactivating NAMPT, a key enzyme in the Salvage Pathway
  • A reversal of biological age by 1.26 years after 28 days of supplementation
  • An increase in the longevity protein SIRT1, a downstream target of NAD+
  • A reduction of inflammatory cytokines indicating that NAD+ is being directed towards beneficial processes rather than inflammatory CD38
  • A reduction in biomarkers of glycation
NAD supplements