Royal Jelly and Its Components Promote Healthy Aging and Longevity: From Animal Models to Humans

Abstract

Aging is a natural phenomenon that occurs in all living organisms. In humans, aging is associated with lowered overall functioning and increased mortality out of the risk for various age-related diseases. Hence, researchers are pushed to find effective natural interventions that can promote healthy aging and extend lifespan. Royal jelly (RJ) is a natural product that is fed to bee queens throughout their entire life. Thanks to RJ, bee queens enjoy an excellent reproductive function and lengthened lifespan compared with bee workers, despite the fact that they have the same genome. This review aimed to investigate the effect of RJ and/or its components on lifespan/healthspan in various species by evaluating the most relevant studies. Moreover, we briefly discussed the positive effects of RJ on health maintenance and age-related disorders in humans. Whenever possible, we explored the metabolic, molecular, and cellular mechanisms through which RJ can modulate age-related mechanisms to extend lifespan. RJ and its ingredients-proteins and their derivatives e.g., royalactin; lipids e.g., 10-hydroxydecenoic acid; and vitamins e.g., pantothenic acid-improved healthspan and extended lifespan in worker honeybees Apis mellifera, Drosophila Melanogaster flies, Gryllus bimaculatus crickets, silkworms, Caenorhabditis elegans nematodes, and mice. The longevity effect was attained via various mechanisms: downregulation of insulin-like growth factors and targeting of rapamycin, upregulation of the epidermal growth factor signaling, dietary restriction, and enhancement of antioxidative capacity. RJ and its protein and lipid ingredients have the potential to extend lifespan in various creatures and prevent senescence of human tissues in cell cultures. These findings pave the way to inventing specific RJ anti-aging drugs. However, much work is needed to understand the effect of RJ interactions with microbiome, diet, activity level, gender, and other genetic variation factors that affect healthspan and longevity.

Keywords: IGF-1; aging; alternative therapy; composition of royal jelly; dietary interventions; healthspan; lifespan; longevity; oxidative stress; royal jelly.

Figure 1

The dynamics of aging-related decrease of healthspan and lifespan. The production of free radicals increases with aging (which is on the rise out of improved disease management) and also with exposure to various stresses (e.g., pollution, poor nutrition, and psychological stress) leading to oxidative stress. This is associated with reduced production of antioxidant enzymes and activation of inflammatory pathways. Both oxidative stress and chronic inflammation lead to a trail of cellular and molecular alterations: telomere attrition, epigenetic alterations, genome instability, reduced proteostasis, disturbed nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Such age-related physiological alterations result in poor health and loss of function out of increased occurrence of various metabolic and neurodegenerative disorders. Age-related disorders are associated with increased mortality and premature death i.e., decreased lifespan.

Figure 2

Royal jelly and its components improve healthspan and extend lifespan in different species.

Figure 3

Probable mechanisms through which royal jelly (RJ) and its components extend lifespan. RJ reduces insulin/insulin-like growth factor-1 signaling (IIS), which heightens the activity of DAF-16—the C. elegans counterpart to the mammalian Forkhead Box O transcription factor (FOXO). Activation of DAF-16/FOXO promotes its translocation from the cytoplasm to the nucleus and fosters interactions with its associated transcriptional co-regulator proteins: host cell factor (HCF-1), sirtuin homologue (SIR-2.1), and FTT-2 (a 14-3-3 protein). This results in formation of protein complex inside cells and enhancement of the expression of multiple longevity promoting genes as well as regulation of downstream process of dietary restriction signaling (which lowers food-intake) and the mechanistic target of rapamycin (mTOR) pathway by extending the lifespan of the control unc-24/+ mutants. The interplay among several genes involved in IIS, mTOR, and dietary restriction signaling boosts key longevity-related cellular processes: DNA repair, autophagy, antioxidant activity, anti-inflammatory activity, stress resistance, and cell proliferation. On the other hand, RJ activates epidermal growth factor receptor (EGFR) signaling mainly by activating its receptor (LET-23). EGFR functions via downstream phospholipase C-γplc-3 and inositol-3-phosphate receptor itr-1 to upregulate elongation factors and chaperonins, which increase protein translation and proteasome activity—a mechanism that entails rebuilding cellular components; enhancement of cellular detoxification, ribosomal function, and muscle maintenance; and reduction of lipofuscin levels (age-pigments that accumulate during senescence).