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Sirtuins, a possible “shield” against Parkinson’s and Alzheimer’s disease

Article by SoLongevity Research
"Longevity proteins" are now the focus of numerous studies that are investigating their possible preventive role against neurodegenerative diseases

What this article is about

  • SIRT genes and their proteins, the sirtuins, have long been known to underlie the processes that regulate aging
  • A review of available studies, published in Neural Regeneration Research, takes stock of studies showing a possible role for sirtuins in preventing neurodegenerative diseases, such as Parkinson’s and Alzheimer’s
  • Several research groups, such as SoLongevity, are developing nutraceuticals for the purpose of stimulating sirtuin expression and helping to prevent age-related diseases

A new path for Parkinson’s and Alzheimer’s prevention?

Sirtuins, the so-called “longevity proteins,” could represent a new pathway against age-related neurodegeneration and play an important role in preventing diseases such as Parkinson’s and Alzheimer’s. Science is paying a lot of attention to the issue, as shown by a literature review conducted by two Italian researchers -David Della Morte Canosci, professor of internal medicine at Tor Vergata University and of neurology in Miami, and Francesca Pacifici, professor of nutrition science at San Raffaele University in Rome- recently published in Neural Regeneration Research.

What are sirtuins and SIRT genes?

The seven SIRT genes which encode sirtuins in mammals (including humans) are among the most highly conserved genes throughout evolution, indicative of their role in regulating functions critical to the survival of cells and organisms, such as cellular respiration and metabolism, programmed cell death (apoptosis) and inflammation. As we have often explained on our website, SIRT genes also underlie the mechanisms that regulate the processes underlyingaging.

Chemically, sirtuins are NAD+ dependent histone deacetylase enzymes. The most studied is sirtuin 1, whose expression can be regulated (among other ways) bycaloric restriction andphysical activity, and has a known anti-aging effect. Simplifying greatly: SIRT1 acts by reducing thelow-grade inflammation and balancing oxidative stress; SIRT2 controls the cell cycle; SIRT3, SIRT4 and SIRT5 are implicated in the metabolic pathways of the mitochondria (the energy powerhouses of cells); SIRT6 aids in the regulation of genomic stability and DNA repair mechanisms; SIRT7 is the only one located in the nucleus of cells and is involved in the process of DNA transcription.

SIRT genes underlie the mechanisms that regulate the processes that cause aging

Sirtuins and neurodegeneration

As the review by the two Italian researchers also reports, it was observed that the mitochondrial sirtuins may have neuroprotective effects against Parkinson’s Disease by regulating, among other things, neuroinflammation and autophagy, the system by which cells “recycle” their unused components and potentially harmful waste (the discovery of the mechanism of autophagy earned the Nobel Prize in Medicine and Physiology for Yoshinori Ohsumi in 2016). SIRT1 also comes into play, because it has been observed that it can reduce the abnormal aggregation of alpha-synuclein, a protein implicated in the disease, which interferes with the communication between neurons and causes their degeneration. SIRT6 also showed a possible preventive role especially againstAlzheimer’s disease.

Sirtuins could play an important role in preventing diseases such as Parkinson’s and Alzheimer’s

What are the micronutrients that activate sirtuins?

Several nutraceutical and pharmaceutical products are currently being studied to activate sirtuins. The one investigated by the two review authors -Della Morte Canosci and Pacifici- is based on the effect of resveratrol, one of the most powerful natural activators of SIRT1. This molecule is found in numerous foods, but it has low bioavailability; therefore other natural molecules, precursors of resveratrol, such as polydatin and pterostilbene, are used. The two scientists have developed a new patented formulation based on polydatin, pterostilbene, honokiol (a polyphenol obtained from plants in the genus Magnolia) and ellagic acid (an antioxidant also of plant origin) along with zinc, selenium, and chromium, which they are testing in models in vitro on Parkinson’s disease cells.

Several nutraceutical and pharmaceutical products are being studied to activate sirtuins

SoLongevity Nutraceuticals.

SoLongevity research has also developed nutraceuticals based on the high-bioavailability precursors of important pro-longevity molecules, such as polydatin andN-acetylcysteine (NAC) (a precursor of glutathione), whose formulation is designed to stimulate sirtuins and balance oxidative stress. Patented formulations include GluRes and GluReNAD: the latter is also a NAD+ booster that can stimulate endogenous NAD+ production and mimic calorie restriction. To learn more, you can visit the nutraceutical section of the SoLongevity website.

Bibliography

Della-Morte, David; Pacifici, Francesca. Nature can still be the strongest help against aging and neurodegeneration: the sirtuins way. Neural Regeneration Research 18(6):p 1271-1272, June 2023. | DOI: 10.4103/1673-5374.360173

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