Resveratrol has long been known as an natural anti-aging gene activator. The target of this activation is SIRT1. Research now indicates that another extract (ursolic acid) is even more powerful than resveratrol in the activation SIRT1. Furthermore, the extracts ursolic acid and rosmarinic acid promote anti-aging in other ways,, including preservation of the functioning of the hypothalamus (implicated as playing a significant role in the aging process), inhibiting fibrosis (amyloid and tau) and inhibiting NOX2 and NOX4.
SIRT1 Activator - Ursolic acid is a powerful activator of anti-aging protein SIRT1. In fact, when compared to resveratol, ursolic acid is double the power of activating SIRT1 versus resveratol.(1)
Hypothalamus Anti-Aging - Recent research indicates that the hypothalamus is an important determinant in longevity, Dysregulation of the hypothalamus during aging affects the neuroendocrine system, and contributes to the exhaustion of stem cells, and the loss of proteostasis.(2) Ursolic acid beneficially supports health of the hypothalamus by enhancing levels of anti-aging SIRT1, SIRT6, PGC-1β and α-Klotho.(3)
Nrf2 Preservation - Nrf2 is the master protein activator of the endogenous antioxidant system in the body, and is related to increased longevity. Ursolic acid is a potent inhibitor of the degradation of Nrf2, which supports increased level of Nrf2. (4)
Longevity Extender - In experimental studies with c. elegans, rosmarinic acid significantly extended lifespan by increasing anti-aging gene expression of daf-16 and other proteins.(5)
NOX2 and NOX4 (NADPH oxidases) Inhibitor - NOX2 and NOX4 play critical roles in aging.
- NOX2 - involved in hypertension, atherosclerosis, cardiac hypertrophy, diabetes and aging. The inhibition of NOX-2 is proposed for maintaining cardiovascular homeostasis.(6)
- NOX4 - involved in cellular senescence. The inhibition of NOX-4 may support anti-aging in body, which is expressed in many organs in the body.(7)
- Both NOXs are viewed as potential therapeutic targets to block.
- Rosmarinic acid inhibits both NOX2 and NOX4.(7)
Amyoid Aggregation Inhibitor - An important hallmark of aging, both in the brain (Alzheimers Disease) and throughout the body, is the formation of amyloid fibril aggregates.
- While resveratrol has been shown to be inactive in the inhibition of aggregate formation, rosmarinic acid, is shown as a powerful inhibitor.(8)
Tau Aggregation Inhibitor - Insoluble tau protein is another protein abnormality (in conjunction with amyloid) associated with Alzheimer's Disease in the brain. Aging and chronic stress may induce tau aggregation. In lab animals, rosmarinic acid was shown to reduce tau protein aggregation. (9)
Glycation Inhibitor - Supports Elastic Arteries and Skin. Glycation is the damaging of protein structure, accelerating aging of all protein structures in the body. Includes loss of elasticity of skin and arterial function.
- Glycation results in stiffness of the skin (and old appearance) and arteries. All indicators of significant aging. Rosmarinic acid was shown to improve the parameters of skin and arterial elasticity in human test subjects.(10)
Insulin Resistance - AMPK. Rosmarinic acid significantly reduced skeletal muscle insulin resistance in insulin resistant lab animals. Rosmarinic acid activated AMPK in the muscle, which resulted in increased mitochondrial biogenesis,(11)
HYPER LONGEVITY (Ursolic Acid | Rosmarinic Acid)
(1) Bakhtian N, et al. Mounting evidence validates Ursolic Acid directly activates SIRT1: A powerful STAC which mimic endogenous activator of SIRT1. Arch Biochem Biophys. 2018 Jul
(2) Kim K, et al. Role of hypothalamus in aging and its underlying cellular mechanisms. Mech. Ageing Dev. 2018. May.
(3) Bahrami SA, et al Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level. Biomed Pharmacother, 2016 Aug
(4) Kamble SM, et al. In silico Evidence for Binding of Pentacyclic Triterpenoids to Keap1-Nrf2 Protein-Protein Binding Site. Comb Chem High Throughput Screen. 2017
(5) Wang F, et al. The Molecular Mechanism of Rosmarinic Acid Extending the Lifespan of Caenorhabditis elegans. Applied Mechanics and Materilals. 2011.
(6) Forte M, et al. The Pathophysiological Role of NOX2 in Hypertension and Organ Damage. High Blood Press. Cardiovasc Prev. 2016 Dec
(7) Revoltella S, et al. Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus. Molecules. 2018 Mar.
(8) Ramazzotti M, et al, Mechanism for the inhibition of amyloid aggregation by small ligands.Biosci Rep. 2016 Sept.
(9) Shan Y, et al. Aging as a Precipitating Factor in Chronic Restraint Stress-Induced Tau Aggregation Pathology, and the Protective Effects of Rosmarinic Acid. J Alzheimers Dis. 2016
(10) Yui S, et al. Beneficial Effects of Lemon Balm Leaf Extract on In Vitro Glycation of Proteins, Arterial Stiffness, and Skin Elasticity in Healthy Adults. J Nutr Sci Vitaminol (Tokyo) 2017
(11) Jayanthy G, et al, Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK. J Cell Biochem. 2017 Jul