**Hiroshi Kunugi <sup>1</sup> and Amira Mohammed Ali 1,2,\***


Received: 3 September 2019; Accepted: 18 September 2019; Published: 20 September 2019

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