Although mitochondria have gained a reputation as the ‘powerhouses of the cell’ due to their energy producing capabilities, they are also now known to be central to healthy aging.

Mitochondrial dysfunction is a key hallmark of aging, with research continuing to show that the decline in mitochondrial number and function as we age contributes to the signs of aging we feel – such as declining energy levels and mental agility. This article will explain why mitochondria are essential for cellular function, the link between mitochondrial function and aging, and how NAD+ supplements can support mitochondrial health.

Mitochondria are dynamic cellular energy factories

Mitochondria are highly dynamic organelles (structures within the cell that have a specialised function), that produce the cellular energy (ATP) that cells need to function. They are not singular entities but rather form networks which can change size, shape and mass, with each cell potentially containing thousands of mitochondria. This means that mitochondrial networks can adapt to the energy requirements of the cell, with organs that have high energy demands, such as the brain or heart, having much higher numbers of mitochondria.

Originally, mitochondria were bacteria which then evolved to work in partnership with cells, eventually becoming dependent upon one another to survive. Now every cell contains mitochondria. As a result, mitochondria have their own DNA (called mtDNA) separate from the DNA found in the nucleus of cells.

Mitochondrial function declines with age

During aging, the number and function of mitochondria decline contributing to the cellular aging process. This occurs for a variety of reasons:

• Increased damage by free radicals – during energy production substances called free radicals are produced. Free radicals are highly reactive and if allowed to accumulate they cause damage to structures within the cell including the mitochondria. The antioxidant pathways which mop-up free radicals also decline with age contributing to mitochondrial damage.

• Decreased mitophagy – mitophagy is the process by which damaged mitochondria are broken down and removed. As mitophagy declines with age, there is an accumulation of dysfunctional mitochondria which can enhance production of free radicals and contribute to inflammation.

• Decreased mitochondrial production – the production of new mitochondria is termed ‘mitochondrial biogenesis’, and this occurs in response to the energy demands of the cell. For example, continuous exercise stimulates mitochondrial production to enhance energy production to meet the energy demand. However, during aging there is a breakdown in communication between the mitochondria and the nucleus. When this occurs, the mitochondria cannot effectively respond to the demands of the cell and the number of mitochondria decline.

Collectively, these changes contribute to mitochondrial dysfunction which is problematic as every cell is critically dependent on healthy mitochondrial function, which ultimately drives healthy aging. So, what can you do to support your mitochondria?

NAD+ and Sirtuins support mitochondrial function

Increasing NAD+ levels and subsequently sirtuin activation, are known to support mitochondrial health. This is because NAD+ and the sirtuins help to prevent many of the issues associated with mitochondrial dysfunction.

NAD+ levels are known to decline by 50% every 20 years and this decline is regarded as a driver of the cellular aging process. NAD+ is essential for energy production in the mitochondria so NAD+ decline contributes to the lack of energy associated with aging. Furthermore, sirtuins need NAD+ to function – without NAD+ sirtuins simply do not work!

There are seven sirtuin proteins located throughout the cell. SIRT3 is found in the mitochondria and activates antioxidant pathways that combat free radicals and protect the cell from damage. SIRT1 and SIRT3 are also known to activate mitophagy via their interaction with key regulatory pathways (e.g. AMPK, FOXO, PGC-1α). Whilst SIRT1 is known to activate PGC-1α, a master regulator of mitochondrial biogenesis, stimulating the production of new mitochondria.

Sirtuins also act as messengers between the mitochondria and the nucleus. In youthful cells they function in perfect harmony, allowing the mitochondria to respond to changes in the cellular environment. However, as sirtuin levels decline, this communication becomes impaired, further contributing to the decline in mitochondrial health.

Overall, research shows the importance of maintaining mitochondrial function to support healthy aging. NAD+ decline is a driver of cellular aging because of its associated decline in sirtuin activation which impacts, among other things, mitochondrial health. Studies show that sirtuins regulate many of the repair and maintenance pathways in the mitochondria which decrease alongside sirtuin activity during aging. Therefore, maintaining NAD+ levels and sirtuin activation should be a priority for those looking to support their mitochondrial health.