Gnosis by Lesaffre (Gnosis) is eager to share the International Journal of Molecular Sciences has published a new study that explores the potential of S-adenosylmethionine (SAMe) to repress the expression of genes that are associated with the pathogenesis of Alzheimer’s Disease (AD). The insights gleaned from this study, which used Adonatâ Premium SAMe, offer promise for protecting against AD-like symptoms later in life due to genetic coding delivered from mother to offspring.

Several previous studies suggested that epigenetic signatures, driving the shift between normal and diseased aging, can be acquired during the first stages of life, even in utero, and manifest phenotypically later in life. In this context, the multidisciplinary team of the Italian University La Sapienza (Rome) investigated whether supplementation with SAMe (as Adonat® Premium SAMe) during the perinatal period (i.e., supplementing the mothers from mating to weaning) could exert a protective role towards the manifestation of AD-like symptoms. Researchers notably assessed the repression of PSEN1 expression, a gene encoding for the Presenilin 1 peptide, which overexpression is associated with amyloid genesis and increased senile plaque burden as well as amyloid deposits in the prefrontal cortex and hippocampus of mice at different ages.

This study suggests that short-term perinatal supplementation with SAMe was as effective in repressing PSEN1 expression and amyloid deposition in adult mice, including size and number of plaques. The results presented in this paper provide fundamental insights at three levels:

  1. Basic knowledge of the epigenetic modulation associated with AD and the perspective of epigenetic treatments for this disease.
  2. The reinforcement of the concept that early-life epigenetic modifiers affect aging.
  3. Epigenetic modifications acquired indirectly (through the mothers by the offspring) in early life are maintained in adults even in the absence of continued supplementation of the modifier.

The authors conclude: “The data presented here strongly support the concept that environmental epigenetic modifiers, such as diet, can effectively drive the aging phenotype when manipulated in early life. Maintaining the proper DNA methylation could be a useful intervention in the prevention or treatment of AD and related dementias… The data contribute to the ‘big picture’ of the role of methylation in AD. The maintenance of DNA methylation patterns, with functional effects on gene expression and through cell generations in the absence of the modifier, is a cellular epigenetic memory that may have a significant impact on physiology and pathology beyond neurodevelopment and neurodegenerative disorders.”

This pioneering study opens the door to many other questions, according to the researchers; notably whether supplementation with SAMe may also modulate other genes expression. The same team had already demonstrated that SAMe could also modulate the expression of BACE1 gene (involved in amyloid processing) in the same mice model, as well as PP2A phosphatase activity (involved in tau phosphorylation; another contributor to the development of AD). However, a lot is still to be explored to better understand the effects exerted by methyl donor supplementation in AD and the potential for such ingredients as therapeutic agents.

The authors also note that it would be worthwhile to check if SAMe supplementation in early life can have higher or even detrimental effects through the modulation of other genes. Moreover, it is a well-established concept that methyl donor availability is essential during preconception and early life to guarantee the proper and healthy development of the embryo.r

“While SAMe supplementation benefits in mood, joint, and liver health are established and continue to be reinforced through published data, scientific breakthroughs, and revolutionary approaches today explore for understanding SAMe’s role in long-term health and longevity through epigenetic regulation and methylation,” says Sophie Legrain-Raspaud, Gnosis Research & Application Director, explaining that as the leading SAMe ingredient producer, Gnosis has long-standing relationships and open collaborations with research institutes to explore how this substance is intimately linked with human health. Among them is a proud collaboration with Prof. Fuso's group at La Sapienza University, with which the company will sponsor the ‘1st Epigenetics Society (ES) International Meeting: Epigenetics of Disease and Development,’ which will be held in Rome, October 12-14, 2023.

“Slowing or averting age-related declines in physical and cognitive health to promote anti-aging effects and longevity can be possible today by taking advantage of the state-of-the-art scientific approach,” adds Legrain-Raspaud. “By going deep inside the mechanisms and the roles of naturally and multi-potent occurring substances like SAMe, we believe we can improve the chances of maintaining optimal health later in life.”