copy 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.

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from ChatGPT:
Royal jelly is a complex mixture of nutrients and bioactive compounds, including proteins, carbohydrates, lipids, vitamins, minerals, and various other substances. Some of the key chemical constituents found in royal jelly that are believed to contribute to its health benefits include:

  1. Proteins and amino acids: Royal jelly contains a variety of proteins and amino acids, including the unique protein royalactin, which is believed to be responsible for many of the benefits of royal jelly.
  2. Fatty acids: Royal jelly contains a range of fatty acids, including 10-hydroxy-2-decenoic acid (10-HDA), which has been shown to have antibacterial and anti-inflammatory effects.
  3. Vitamins and minerals: Royal jelly is a rich source of vitamins and minerals, including B vitamins, vitamin C, vitamin E, calcium, potassium, and iron.
  4. Sugars and carbohydrates: Royal jelly contains various sugars and carbohydrates, including glucose, fructose, and sucrose.
  5. Nucleic acids: Royal jelly contains nucleic acids, such as DNA and RNA, which are important for cellular function and may help to support healthy aging.
  6. Phenolic compounds: Royal jelly contains phenolic compounds, including flavonoids and phenolic acids, which have antioxidant and anti-inflammatory properties.
  7. Enzymes: Royal jelly contains various enzymes, including catalase, which helps to protect cells against oxidative stress.

These and other constituents found in royal jelly are believed to contribute to its potential health benefits. However, more research is needed to fully understand the mechanisms behind these effects.

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RJ basically increases the level of gene expression. I would assume the genes are longer ones. This creates the queen phenotype. My own hypothesis is that most phenotypic changes of aging result from lower gene expression. This is mainly caused by a reduction in acetyl coa levels. RJ includes b5 which is a coa precursor and also the 10-hydroxy-2-decenoic acid which is an HDAC inhibitor. It is however a weak HDACi operating in the millimolar range.

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This is a good paper from 1948

I think he is wrong about the other parts of RJ and later papers found the HDACi effect was significant. I think nucleic acids and particularly RNA levels are also significant as this provides the raw material for RNA Polymerase II and hence means it is less likely to be terminated incorrectly.

Thomas Gardner did a lot of good early work on Longevity.

The other thing to look at is hibernation. That in essence is the opposite effect where acetylation is reduced and fewer proteins are produced. My thesis is that many of the hallmarks of aging are caused by a gradual process which has similarities to hibernation. Which does not reverse in the spring though.

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What we need is royal jelly designed for humans. What would that look like? It’s hard to imagine that bees are a good model for human interventions. A mouse has to be much better than a bee.

Does the queen bee eat mostly royal jelly during its lifespan? That’s one hell of a supplement.

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Royal Jelly has two key components that have epigenetic effects.

10-HDA

This is a relatively weak Histone Deacetylase Inhibitor it operates in the millimolar range.

and

Vitamin B5. (Pantothenic Acid)

Vitamin B5 is a precursor of Coenzyme A. ACLY and ACCS2 are enzymes that create Acetyl-CoA from citrate and acetate respectively. Hence Royal Jelly has B5 in it to ensure that Acetyl-CoA is created.

Hence a human equivalent of royal jelly might include various Histone Deacetylase Inhibitors, Vitamin B5 (and it really also needs B12) and some citrate. (ACCS2 is only mildly useful as it is inhibited by acetylation). I also add some extra RNA.

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By citrate, do you mean citric acid?

No. Citric acid is acidic and drinking a lot of lemon juice is not a good idea. If you react citric acid with sodium hydroxide you get sodium citrate which is mildly alkaline.

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Thanks for that. I’ll keep my eye on this topic. Vit B5 and Citrate.

Would Magnesium or Potassium Citrate be equally good?

You need a mixture of cations, but it is best to read another thread

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Going to try the MNT powder with Pterostilbene and sulforaphane.

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Effects of royal jelly consumption on clinical outcomes in patients with ischemic stroke: A triple-blind randomized controlled trial

Abstract

The therapeutic impact of royal jelly (RJ) consumption in patients with ischemic stroke is unknown. Therefore, we conducted a randomized, triple-blind, placebo-controlled clinical trial to evaluate the role of RJ supplementation on clinical and biochemical outcomes in patients recovering from ischemic stroke. Out of 64 enrolled patients (45–80 yrs.) with ischemic stroke, 32 were randomized to the RJ group and 32 to the placebo (control) group. Groups completed a 12-week intervention. The intervention group received 1000 mg/d of RJ dragee after breakfast. We evaluated stroke-related disability, quality of life, and inflammatory and oxidative stress markers at baseline and post-intervention. At post-intervention, serum levels of erythrocyte sedimentation rate decreased in the RJ group compared to the control group (adjusted mean difference, −8.65 mm/h [95 % CI, −14.75 to −2.55]). Additionally, serum nitric oxide levels increased in the RJ group (adjusted mean difference, 10.18 nmol/mL [95 % CI, 0.51 to 19.86]) post-intervention compared to the control group. Furthermore, the RJ group exhibited a decreased oxidative status index (adjusted mean difference, −0.003 [95 % CI, −0.006 to −0.0001]) and reduced odds of stroke-related disability (adjusted odds ratio, 0.20 [95 % CI, 0.05 to 0.70]) compared to the placebo group. Moreover, RJ supplementation improved the quality-of-life measures in the RJ group (adjusted mean difference, 16.64 [95 % CI, 1.17 to 32.12]) compared to the control group. Our findings reflect the potential benefits of RJ consumption on clinical and biochemical outcomes of patients recovering from ischemic stroke. Importantly, we acknowledge the necessity of additional studies to verify the efficacy of RJ supplementation in patients recovering from strokes.

I think this is something where eating a higher dose than 1g per day would be more effective. Queen Bees exist on it.

It is a mixture including a weak HDAC inhibitor, some AMPK activation and a coenzyme-A precursor (B5).

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Iranian paper, in mice but… Royal jelly improves learning and memory deficits in an amyloid β-induced model of Alzheimer’s disease in male rats: Involvement of oxidative stress 2023

Royal Jelly has some impressive results:
https://genomics.senescence.info/drugs/drug_details.php?compound_name=Royal%20Jelly

How come it’s never been tested in the ITP? Too expensive?

Here they claim that the human equivalent of royal jelly is a protein (NHLRC3) that they named “Regina”: Honey bee Royalactin unlocks conserved pluripotency pathway in mammals 2018

“Royal jelly is the queen-maker for the honey bee Apis mellifera, and has cross-species effects on longevity, fertility, and regeneration in mammals. Despite this knowledge, how royal jelly or its components exert their myriad effects has remained poorly understood. Using mouse embryonic stem cells as a platform, here we report that through its major protein component Royalactin, royal jelly can maintain pluripotency by activating a ground-state pluripotency-like gene network. We further identify Regina, a mammalian structural analog of Royalactin that also induces a naive-like state in mouse embryonic stem cells. This reveals an important innate program for stem cell self-renewal with broad implications in understanding the molecular regulation of stem cell fate across species.”

We next wondered whether a homolog of Royalactin existed in mammals. Sensitive searches of sequence databases using iterative PSI-BLAST23, as well as aiming HHPRED sequence and structural profiles against the human and mouse proteomes24 did not reveal any Royalactin orthologs. However, the latter computational tool revealed that Royalactin is distantly related to an existing structure in the PDB database25, a secreted salivary gland protein (SGP) from the sand fly, L. longipalpis (PDB ID: 3Q6K)26. We then used this structure––a six-bladed β-propeller fold with no additional domains—as an accurate template for MODELLER27, yielding a high confidence model for the Royalactin fold (Fig. 3a). The resulting superposition of Royalactin and SGP sequences was then used to seed new and more precise HHPRED scans of the human proteome, in search of a possible structural and functional analog of the Royalactin/SGP β-propeller fold. Fitting the description of a secreted, single domain chain, with a predicted 6-bladed β-propeller architecture, only one protein, the provisionally named NHL Repeat Containing 3 (NHLRC3), arose as a potential candidate, with striking fold similarity to the Royalactin model (Fig. 3a). Although no known function of NHLRC3 has been identified to date, single-cell RNA-seq analyses of early mouse embryos revealed that it is expressed starting in E4.5 embryos, and that its expression increases steadily thereafter (Supplementary Figure 3a). To elucidate whether it served a functional purpose in stemness maintenance in mESCs similar to that observed with Royalactin, recombinant mouse NHLRC3 was added to mESC culture in the presence of serum/–LIF (serum/–LIF + NHLRC3) as well as 0i (0i + NHLRC3). As seen with Royalactin, NHLRC3 maintained mESCs in an undifferentiated state in both culture conditions for multiple passages (Fig. 3b, c, Supplementary Figure 3b, c), with expected changes in gene expression (Fig. 3d, e). Additionally, injection of 0i + NHLRC3 cultured cells into mouse blastocysts generated chimeric animals with germline transmission, highlighting the robust effects of this protein in vivo (Supplementary Figure 4, Supplementary Table 1). Thus, NHLRC3 appears to be a mammalian pluripotency maintenance factor, whose existence demonstrates a remarkable conservation of macromolecular structure and function. We renamed NHLRC3 as Regina due to its conservation of functions with those of Royalactin and the queenmaker Royal Jelly.

Have you looked at “Regina” @John_Hemming?

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RJ as i see it is a combination of a weak HDAC inhibitor, an AMPK activator and a CoA precursor. It seems to drive an alternative phenotype in hymenoptera which strikes me as an alternative splicing. I am currently of the view that bees particularly go through a phase where their splicing development clock is set to queen, but only queens stay there.

For human beings I think a different approach is needed rather than chugging RJ.

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