NAD+ and the Hallmarks of Aging

Our previous article detailed the nine Hallmarks of Aging, how they impact cellular health, and contribute to the aging process. This article describes how increasing cellular NAD+ levels with NAD+ supplements can positively impact all of the Hallmarks of Aging and subsequently be used as a tool to slow biological aging.

The Hallmarks of Aging are Interconnected

Aging is an example of how complex biology can be. While each hallmark is described as a distinct issue, in reality, all of the hallmarks of aging are highly interconnected. This means that if you want to slow the cellular aging process, multiple hallmarks need to be addressed simultaneously.
This highlights the need for a multi-target approach. Just targeting one hallmark will have little to no impact on aging, but a multi-target approach can offer significant benefit.

NAD+ and the hallmarks of aging


NAD+ restoration has been identified as a multitarget approach which can positively impact all of the Hallmarks of Aging. This means NAD+ restoration provides a unique opportunity to both restore optimal cellular function and slow age-related decline across the whole body.


NAD+ is a tool to slow Biological Aging

NAD+ is a critical coenzyme found in every cell of the body, meaning its presence is required for cellular reactions to occur.  NAD+ is involved in around 500 biochemical reactions including many that have important implications for the Hallmarks of Aging. 

Unfortunately, it has been found that cellular NAD+ levels decline with age, by around 50% every 20 years, which negatively impacts each of the Hallmarks of Aging in the following ways: 

Genomic instability

  • Adequate NAD+ availability is critical to drive important DNA repair enzymes and pathways such as PARP1, SIRT1, and SIRT6.
  • Conditions associated with premature aging have been found to have reduced NAD+ levels and DNA repair capability.

Cellular Senescence

  • Low NAD+ promotes senescence in skin whilst restoration of NAD+ reduces the number of senescent cells.
  • High levels of NAD+ promote cellular repair, preventing the accumulation of cellular damage which causes cellular senescence to occur in the first place.
  • Senescent cells secrete inflammatory factors which increase expression of CD38 (a large NAD+ consumer) ultimately contributing to its decline.

Epigenetic Alterations

  • NAD+ is critical for the activity of the sirtuins which are key regulators of cellular health.
  • The sirtuins activate many beneficial longevity pathways by promoting youthful epigenetic regulation and gene expression.
  • Reduced NAD+ means sirtuins cannot perform this critical role, contributing to altered gene expression during aging.
  • The decline in NAD+ / sirtuins and the impact this has on epigenetic expression is a key part of Professor David Sinclair’s ‘Information Theory of Aging’.

Mitochondrial Dysfunction

  • Adequate NAD+ is critical for maintaining mitochondrial health and supporting optimal mitochondrial function.
  • Via its interaction with sirtuins, NAD+ regulates:
    • Mitochondrial biogenesis (production of new mitochondria)
    • Mitophagy (the recycling of damaged mitochondria)
    • Stress resistance and mitochondrial repair pathways

Telomere Attrition

  • NAD+ restoration is found to alleviate telomere dysfunction.

Altered Cellular Communication

  • NAD+ and Sirtuins help regulate appropriate activation of pro-inflammatory pathways.
  • The loss of NAD+/Sirtuins contributes to chronic inflammation during aging (inflammaging).

Loss of Proteostasis

  • NAD+ is required for activation of autophagy to clear damaged cellular proteins.
  • NAD+ is also necessary for activation of the unfolded protein response which regulates the quality of mitochondrial proteins.

Deregulated Nutrient Sensing

  • NAD+ levels are critical to sense the energy status of the cell and for adaptation to energy stress.
  • NAD+ decline impairs the nutrient sensing pathways AMPK, Sirtuins and PGC-1α which are critical for normal metabolism.

Stem Cell Exhaustion

  • NAD+ restoration and sirtuin activation leads to stem cell rejuvenation.


The potential of NAD+ restoration to impact multiple Hallmarks of Aging simultaneously to slow cellular aging is due to its pivotal role in a wide variety of cellular functions as described. With a variety of products available to boost NAD+ it is important to choose products which address the root causes of NAD+ decline such as Nuchido TIME+.