Sirtuin Activation & Anti-Aging
The link between NAD+ and the aging process is well established but it is actually NAD’s role in activating a specific group of proteins that result in the beneficial anti-aging effects we associate with NAD. This family of proteins are called sirtuins and they are so essential to slowing the aging process, they are often referred to as the ‘longevity genes’.
Understanding the activation of sirtuins and the role this plays in slowing the aging process is, therefore, highly relevant to any antiaging approach.
What are Sirtuins?
Sirtuins are a family of seven proteins numbered SIRT1 through 7 and are found in all cells. They are essential to cellular health, energy metabolism and the regulation of gene expression. Their job is to remove acetyl ‘markers’ from specific sites on the DNA which changes its structure and, consequently, its activity.
Scientific evidence shows that sirtuins have always been present in humans. They are ancient proteins which have been conserved throughout evolution. Sirtuins are found in various compartments within the cell, allowing them to target a variety of different proteins involved in metabolism, DNA repair, mitochondrial biogenesis, and cellular deterioration. Of the seven sirtuins SIRT1 is the most studied and mediates many of the favourable effects.
SIRT1 allows the cells to protect themselves in response to cellular stress and is vital for neuronal protection. This is especially important in cells such as neurons and cardiac muscle cells. SIRT1 is also involved in fulfilling the energy demands of our muscles. Activation of SIRT1 enables the muscles in the body to repair themselves and maintain their structure.
Activation of Sirtuins by NAD
Whilst sirtuins are involved in the regulation of many fundamental biological processes throughout the body, all of these activities require the initial activation of the relevant sirtuin. Furthermore, all of these activation mechanisms depend specifically on NAD+; the benefits of sirtuins cannot be harnessed without the presence of NAD+.
NAD+ itself is manufactured within the cell and can be made through different mechanisms, including by recycling the waste products from used NAD within the cell. This recycling mechanism is called the salvage pathway. The salvage pathway is of particular interest in the context of aging as it is the cell’s original and youthful way of maintaining high levels of NAD.
However, it is well established that as we age our NAD+ levels decrease by 50% every 20 years. Therefore, it is not surprising that sirtuin activation declines at the same rate. This leaves cells more vulnerable to cellular damage and less able to repair itself. Cells don’t function to the extent and in the manner that they should and, eventually, physical symptoms occur.
Sirtuins and Aging
It is thought that sirtuin depletion occurs due to two main reasons.
Firstly, the increased levels of DNA damage within older cells chronically activates the family of proteins required to repair and manage this damage. This group of proteins are known as PARPs. PARPs consume vast amounts of NAD in order to do their job and, as a result, NAD is depleted and the activation of sirtuins is reduced.
Secondly, the decline in function of the circadian rhythm associated with increased age results in decreased NAD synthesis. This impacts the various cellular processes that sirtuins help to regulate particularly, cellular stress management and metabolism.
Activating Sirtuins
Following studies in yeast, mice, and mammals, sirtuin activation can support longevity, improved DNA repair, regulation of reactive oxygen species, and energy metabolism. All of which are cellular functions that become less efficient with age.
A non-therapeutic method of activating sirtuins is via calorie restriction such as intermittent fasting. Calorie restriction increases NAD levels in the liver, muscle and adipose tissues resulting in an activation of sirtuins. The link between calorie restriction, sirtuin activation and increased longevity has been well characterized in mammals.
Another non-therapeutic approach is exercise. Several scientific studies have shown that exercise can increase both NAD levels and SIRT1 activation. In fact, after several sessions of exercise, an increase in mitochondrial energy production and antioxidant function was observed.
Increasing the activation of sirtuins by replenishing NAD+ within the cells can also be achieved by supporting the pathways for NAD+ synthesis. A number of ingredients have been identified to have a positive effect on restoring the cells ability to make and recycle NAD+. Evidence suggests that, by combining these ingredients, a whole system approach can be achieved resulting in sirtuin activation.