Stem Cell Renewal : Anti-Aging Perspectives

13 - 04 - 2022

Damaged and senescent cells in our tissues and organs are constantly replaced by new ones, derived from the activation of stem cells – undifferentiated multipotent cells known for their ability to self-renew and differentiate into various functional cell types. However, with age, stem cells become less and less active – a process that contributes to the regeneration defects associated with ageing. These malfunctions lead to degeneration of certain tissues or organs and ultimately to systemic deterioration.

Stem cells constantly call upon their mitochondria – intracellular organelles – to meettheir energy needs. However, these mitochondria weaken over time, thereby reducing the regenerative potential of stem cells.

The molecular chains regulating the function of mitochondria have been identified. One compound, nicotinamide dinucleotide (NAD) – an essential cofactor for many cellular processes – was found to be missing. Replacing old and damaged mitochondria with perfectly healthy new ones requires the presence of sirtuinsdeacetylases known for their effects onhealthandlongevity – which are themselves dependent on NAD for their synthesis and function. The drop in NAD levels with age therefore has a direct impact on sirtuins and thus on mitochondria, accelerating ageing.

Fortunately, these processes can be reversed, thus offering the possibility ofkeeping regenerative capacities intact. Appropriate supplementation canimprove mitochondrial function and reactivate cell regeneration – a promising way to maintain the capacity of existing stem cells.

Although far from useless, NAD supplementation is not the best option, as it is converted by intestinal enzymes into nicotinamide mononucleotide (NMN) and then into various metabolites, including nicotinamide riboside (NR), a precursor of NAD that is highly absorbable and bioavailable after ingestion. In order to avoid several successive degradation and synthesis steps, direct supplementation with NR is generally preferred. This type of supplementation allows a rapid restoration of cellular NAD levels necessary for the proper functioning of stem cells. High levels of NAD protect tissues and reduce the risk of age-related diseases such as cognitive decline, metabolic and cardiovascular diseases – thereby ensuring health and longevity.

A synergistic effect can be achieved by combining the restoration of NAD levels with supplementation of resveratrola plant polyphenol known to stimulate sirtuin activity – ensuring that the restored sirtuin activity can have maximum impact on health and ageing.

These anti-ageing strategies offer real prospects.

Disclaimer : This information is provided for guidance only and is not a substitute for medical advice.

 

References :

Zhang H, Ryu D, Wu Y, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 2016;352(6292):1436-1443.

Wu LE, Sinclair DA. Restoring stem cells – all you need is NAD+. Cell Res. 2016;26(9):971-972.

Baumann K. The yin and yang of mitochondrial dysfunction. Nat Rev Mol Cell Biol. 2016;17(6):331.

Garrido A, Djouder N. NAD+ Deficits in Age-Related Diseases and Cancer. Trends Cancer 2017;3(8):593-610.

Imai SI, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471.

Yaku K, Okabe K, Nakagawa T. NAD metabolism: Implications in aging and longevity. Ageing Res Rev. 2018;47:1-17.

Lee SH, Lee JH, Lee HY, et al. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019;52(1):24-34.

 

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