SENESCENT REGULATOR

Senescent Regulator serves to offer next level support through cutting-edge key compounds, including pterostilbene, resveratrol, luteolin, and curcumin, that have been shown to support autophagy.

Autophagy is a cellular process that is essential for maintaining cellular homeostasis and preventing age-related diseases. The process involves the degradation and recycling of damaged proteins and organelles, which helps to prevent the accumulation of cellular waste and the formation of senescent cells, often referred to as Zombie Cells. It accomplishes this through five main mechanisms: clearance of damaged cellular debris, regulation of reactive oxygen species (ROS), metabolism of misfolded proteins, regulation of cellular metabolism and supporting genomic stability.

Resveratrol & Pterostilbene

Pterostilbene and resveratrol support SIRT1, a protein that plays a critical role in regulating autophagy.^1,2 One of the ways that SIRT1 regulates autophagy is by deacetylating and activating the transcription factor forkhead box O (FOXO) family of proteins. FOXO proteins are involved in the regulation of autophagy-related genes, including LC3 (microtubule-associated protein 1 light chain 3) and Beclin-1, which are critical for the initiation and progression of autophagy. They also modulate the AMPK/mTOR pathway, supporting healthy levels of oxidative stress.³

Luteolin

Luteolin, which is rich in foods such as celery, parsley, apple skins, cabbage and broccoli, can induce autophagy by modulating signaling pathways, regulating autophagy-related genes, reducing cellular stress, and activating transcription factors. Signaling pathways luteolin works on are AMPK and mTOR.⁴ Similar to pterostilbene and resveratrol, Luteolin regulates Beclin-1 and LC3-I but also aids Atg5, which is responsible for initiating the natural processing of damaged cells and organelles.⁵

Curcumin (as CurcuPrime^® Tetrahydrocurcumin & TurmiPure Gold^® Turmeric Extract)

Curcumin works in much the same way in terms of pathways and mechanisms, however in addition to promoting AMPK and the expression of autophagy-related genes it also addresses two additional areas: cellular stress and lysosomal function.^6,7 Curcumin has been shown to support healthy levels of oxidative stress, which can promote autophagy. By helping to maintain healthy levels of lysosomal function, curcumin can help initiate the clearance of cellular waste created during the energy production process as well as aiding the activity of lysosomal enzymes.

CurcuPrime®, which is tetrahydrocurcumin (4HC), is a major curcuminoid metabolite of curcumin, naturally occurring in turmeric. This 4hc provides potent antioxidant properties, supporting autophagy and cellular renewal all while contributing to metabolic, cardiovascular and neurological health.

TurmiPure Gold® Turmeric Extract is a highly concentrated water dispersible form of curcumin, that demonstrated a 24x higher bioavailability than standard 95% curcumin. Ideal for a range of system support at a far lower dose than is typically needed.

Supporting autophagy with these natural compounds has several potential health benefits, including supporting neurological function, immune system regulation and setting the stage for longevity and optimal healthspan. For example, a study found that resveratrol can support cognitive function in older adults by promoting autophagy in the brain.8 Another study found that stilbenes have a potentially supportive role involving glucose and insulin metabolism via various cellular and subcellular mechanisms including GLUT4 upregulation and insulin receptors sensitization.⁹

In addition to supporting autophagy, these natural compounds can also help to minimize senescent cell formation. A study found that pterostilbene can reduce the number of senescent cells in the liver of mice by promoting autophagy. Another study found that resveratrol can reduce the accumulation of senescent cells in the skin of mice by promoting autophagy.

By promoting and ongoing, consistent process of autophagy with Senescent Regulator and supoorting SIRT1, modulating the AMPK/mTOR pathway, mitigating oxidative stress, and regulating autophagy-related genes, individuals are ideally positioned for promoting overall health and longevity.

1. Fang Y , Wang X, Y ang D, Lu Y , Wei G, Y u W, Liu X, Zheng Q, Ying J, Hua F. Relieving Front Aging Neurosci. 2021 Sep 20;13:738686. doi: 10.3389/fnagi.2021.738686. PMID: 34616289; PMCID: PMC8489683.

2. Cheng Y , Di S, Fan C, Cai L, Gao C, Jiang P , Hu W, Ma Z, Jiang S, Dong Y , Li T, Wu G, Lv J, Y ang Y . Apoptosis. 2016 Aug;21(8):905-16. doi: 10.1007/s10495-016-1258-x. PMID: 27270300.

3. Chen CC, Jeon SM, Bhaskar PT, Nogueira V , Sundararajan D, Tonic I, Park Y , Hay N. Dev Cell. 2010 Apr 20;18(4):592-604. doi: 10.1016/j.devcel.2010.03.008. PMID: 20412774; PMCID: PMC3031984.

4. Liu, Y ., Huang, J., Zheng, X. et al. Sci Rep 7, 7877 (2017). https://doi.org/10.1038/s41598-017-08204-6

5. Lee HS, Park BS, Kang HM, Kim JH, Shin SH, Kim IR. Medicina (Kaunas). 2021 Aug 26;57(9):879. doi: 10.3390/medicina57090879. PMID: 34577802; PMCID: PMC8470580.

6. Perrone L, Squillaro T, Napolitano F, Terracciano C, Sampaolo S, Melone MAB. Nutrients. 2019 Aug 13;11(8):1881. doi: 10.3390/nu11081881. PMID: 31412596; PMCID: PMC6723827.

7. Zhang J, Wang J, Xu J, Lu Y , Jiang J, Wang L, Shen HM, Xia D. Oncotarget. 2016 Nov 15;7(46):75659-75671. doi: 10.18632/oncotarget.12318. PMID: 27689333; PMCID: PMC5342768.

8. Wang N, He J, Pan C, Wang J, Ma M, Shi X, Xu Z. Front Neurosci. 2019 Aug 20;13:859. doi: 10.3389/fnins.2019.00859. PMID: 31481868; PMCID: PMC6710371.

9. Shazmeen, Haq IU, Rajoka MSR, Asim Shabbir M, Umair M, Llah IU, Manzoor MF, Nemat A, Abid M, Khan MR, Aadil RM. Food Sci Nutr. 2021 Sep 13;9(11):6389-6405. doi: 10.1002/fsn3.2553. PMID: 34760269; PMCID: PMC8565239.