Copy of NAD+ in ageing and longevity

Copy of NAD+ in ageing and longevity

Given the critical function of NAD+ in maintaining cellular health it would be expected that the body would have a consistent supply of it throughout human lifespan. This is not the case, as NAD+ levels actually decline by approximately 50% every 20 years in humans. Age-related decline of NAD+ and sirtuin activity is a key driver of the cellular ageing process. As cells cannot function or repair properly, cellular damage accumulates ultimately causing the signs and symptoms of ageing we see and feel. [1]

Studies show that age-dependent NAD+ decline is observed across all species and in several human tissues including the skin, liver, brain, skeletal muscle and immune cells. NAD+ depletion is also observed in diseases associated with accelerated ageing, such as xeroderma pigmentosum group A and Cockayne Syndrome. [2-5]

Ageing begins at the cellular level

Ageing is scientifically defined as the loss of the body’s innate ability to repair and regenerate itself, allowing the accumulation of cellular damage. This results in cellular dysfunction, causing the signs and symptoms of ageing. It is now widely accepted that all of the external manifestations that we associate with ageing such as frailty, fatigue and wrinkles, ultimately result from dysfunction at the cellular level. [6,7]

While humans are living longer than ever before, a significant portion of later life is burdened with age-related diseases. By treating the ageing process itself, the goal is to extend healthspan – the portion of life lived in good health, free from frailty and disease. Globally current lifespan has increased and is now 73 compared to just 47 years old in the 1950’s. However, we have failed to proportionally increase healthspan and the global healthspan is only 64 meaning on average there is a 9-year period in which people are suffering from age-related diseases. [8,9]

What causes cellular ageing?

Ageing is a biologically complex phenomenon, but research has now revealed the 12 key cellular changes that underpin the ageing process. These cellular changes are termed the ‘Hallmarks of Ageing’.  [7]

In the context of skin ageing, the histological changes that occur, such as a loss of collagen, elastin and a breakdown of the extracellular matrix (the scaffolding structure of the skin), are a result of the underlying cellular hallmarks of ageing. [10]

These include genomic instability arising from failure to repair UV-induced DNA damage, reduced cell turnover due to mitochondrial dysfunction, degradation of the extracellular matrix due to chronic low-grade inflammation and decreased production of collagen and elastin as a result of senescent fibroblasts. [11]

The discovery of these hallmarks has fundamentally changed our view and approach to treating ageing, and current research is focused on finding treatments that target these hallmarks to restore youthful cellular function.

NAD+ slows cellular ageing

NAD+ has emerged as a healthy ageing tool because it targets all of the Hallmarks of Ageing. Therefore, restoration of NAD+ has a multitude of benefits. At the cellular level, NAD+ restoration improves mitochondrial function, enhances DNA damage repair, increases ATP production and activates. At a whole-body level, boosting NAD+ has been demonstrated to restore age-associated muscle loss, increase endurance and strength, increase neurogenesis, enhance cognitive function and improve markers of metabolic health, all of which positively impact healthspan. [12-15]

NAD+ has also emerged as a potential therapeutic tool for several age-related diseases which are associated with NAD+ deficiency. These include metabolic disease, neurodegenerative disorders, liver disease, kidney diseases and cardiovascular diseases. [16-23] The diverse protective and regenerative capacity of NAD+ is attributed to its involvement in restoring optimal function at the cellular level, by preventing and reversing the hallmarks of cellular ageing.

Ageing can be measured

All this research led to the concept of ‘biological ageing’ – the decline in cellular processes that result in the ageing process.  Unlike chronological age, which is simply the amount of time since birth, biological age is the true age at which the cells and the body are functioning. [24]

Surprisingly, it has been found that the rate at which cells age isn’t as closely linked to chronological age as first thought. [25] For example, a person may be forty years old chronologically, but they could have a biological age that is closer to fifty. This is because biological age not only reflects genetics, but also the accumulated effect of lifestyle factors such as diet and exercise. [26]

The difference between chronological age and biological age is therefore a good measure of how well a person is ageing inside. This has led to the development of ‘biological age clocks’ that predict a person’s biological age. These work on the basis that older cells have a pattern of genes and protein markers that are distinct to younger cells and the shift from a young to old pattern seems to happen in a predictable and measurable way. [27] Biological age has been found to be associated with increased risk of developing almost every chronic disease and reversing biological age can improve healthspan. [28

The discrepancy between biological and chronological age, highlighted to scientists that there was opportunity to intervene at the cellular level to improve ageing and studies now demonstrate that biological ageing is indeed reversible. [29]

There is now unequivocal evidence that ageing begins at the cellular level and it is a highly malleable process. Just as it can be accelerated it can also be reversed. Exciting developments in the longevity space mean that we can now measure how well our cells are ageing with a simple test and commonly available treatments such as NAD+ restoration have the power to reverse biological age.

References

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  2. Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., & Guillemin, G. J. (2012). Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.
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