Search for a drug with anti-aging properties and the promise of immortality has been a dream of human beings for centuries. From “Elixir of life” in the western world to the Chinese Alchemy sought by the first emperor of Qin Shi Huang, magic potions promising immortality was one of the most researched drugs of all time and yet was never discovered. Life expectancy at birth are different for each country when considering that various factors contribute to the longevity (Figure 1) [1]. Major factors considered are genetics, diet and exercises as well as environmental factors and availability of good healthcare. Twin studies have estimated that approximately 20-30% of the variation in human lifespan can be related to genetics, in other words, 70-80% are related to environmental factors [1]. Genetic factors include the diversity in the activities of DNA repair proteins, telomerase, and susceptibility to critical diseases such as cancer and cardiac failure. The definition of death is defined as death of brain function in modern medicine. Maintaining brain function, notwithstanding other types of organ failure, is critical to living longer.
Researchers at CureScience™ Institute are currently focusing on neurodegenerative disorders. As we age, neurons are damaged by oxidative stress and imbalanced metabolism; degenerated neurons will lead to diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis as well as neurological conditions of traumatic lesion and stroke. Herbal medicines have scientific relevance in the treatment of these pathogenesis. One of these Chinese herbal substances, Astragaloside IV (AS-IV) demonstrated significant neuroprotective properties (2). Treatment of cells in rodent animal models of Parkinson’s disease with AS-IV increased cell survival, reversed the intracellular generation of reactive oxygen species, inhibited Bax-mediated apoptosis, and mitigated the loss of dopaminergic neurons. In Alzheimer’s disease, the aggregation of the amyloid protein Aß and tau protein leads to a progressive degeneration of neurons resulting in damage to the memory, cognitive awareness and behavior. Treatment of Alzheimer’s disease in animal models with AS-IV improved neuronal survival by reducing reactive oxygen species and superoxide dismutase generation as well as reduced the number of apoptotic cells by regulating the release of caspase-3 and cytochrome c. AS-IV has also been tested in rat models of the experimental autoimmune encephalomyelitis, which is the animal model of multiple sclerosis. The drug prevented the infiltration of inflammatory cells and decreased oxidative stress. These neuroprotective effects extended life expectancy of animal models significantly. More recently, a double-blind, randomized, controlled clinical study of Astragalus on hemorrhagic stroke victims demonstrated that AS-IV improved the functional recovery of patient with minor adverse effects [2]. These results show that anti-oxidant and anti-apoptotic effects of the drug protect neurons and mitigate many of neurodegenerative diseases. CureScience™ continues its search for such effective drugs derived from natural compounds as well as chemical compounds.
As previously mentioned, another major factor defining longevity is diet. The reduction in the intake of calories without concurrent malnutrition defined as caloric restriction (CR), seemed to be ~15% favorable against mortality during aging. CR reduces the release of growth factors like growth hormone, insulin, and insulin-like growth factor 1 (IGF1), which have been shown to accelerate aging and increase mortality. A recent study demonstrated that mice with transgenic overexpression of fibroblast growth factor 21 (FGF21), fasting hormone, have extended lifespans when maintained on an ad libitum diet [3]. In another study, lack of Klotho proteins in mice showed phenotype of aging such as kyphosis and die earlier [4]. These Klotho proteins are required for binding of FGF19, FGF21 and FGF23 to their cognate fibroblast growth factors (FGF) receptors, which are believed to be involved with longevity. For example, FGF19, the satiety hormone secreted from the intestine was found to bind to bKlotho-FGF-R4 complex to promote metabolic response to feeding. By contrast, under fasting conditions, the liver secretes the starvation hormone FGF21, which induces metabolic responses to fasting, activating the hypothalamus-pituitary-adrenal axis, following binding of FGF21 to bKlotho-FGFR1 complex. These results suggest that there is a close correlation of diet to aging. Klotho proteins are now available from the company “Klotho Therapeutics”.
Indian Gooseberry “Amla” is also well known for superfood to support immortality in Ayurveda. Amla fruit is a rich source of antioxidants and vitamin C, good for control of diabetes, digestion, mental health, weight loss and hair health. Taken together continuous supply of anti-oxidant and control of diet may be key factors to support longevity.
Written by: Misa S. Anekoji, Ph.D.
Keywords: Antiaging, Longevity, Antioxidant, FGF, Diet, Neurodegenerative Diseases
References:
1. https://en.wikipedia.org/wiki/Longevity
2. “Astragaloside IV supplementation promotes a neuroprotective effect in experimental models of neurological disorders: a systematic review.” I.M.Costa et al., Current Neuropharmacology, 17:648-665 (2019)
3. “The search for antiaging interventions: from elixirs to fasting regimens”. R. de Cabo et al., Cell, 157:1515-1526 (2014)
4. “The Klotho proteins in health and disease” M . Kuro-o. Nature Reviews Nephrology, 15:27-44 (2019)