(Aging as a result of stress, fitness, etc)
Though not specifically proven by science, many people claim Gen Z are indeed aging more rapidly than previous generations like millennials. I have a few reasons why this may be the case.
High Intake of sugar and ultra-processed foods. Thanks to food delivery apps like DoorDash and Uber Eats fast food is more convenient than ever. These foods are high in inflammatory PUFA (mainly in the oils they are cooked in), sodium (increases water retention in the face making you look older), and high glycemic carbs (which decrease collagen and promote the formation of AGEs). Many Gen Z also do not know how to cook food leading to an overreliance on premade processed foods.
Higher stress levels. Gen Z has some of the highest rates of anxiety and depression. I believe this is due to several reasons. Lack of good sleep due to electronics. Poor diet as stated before. Lack of social avenues to meet new people and form a community thanks to social media (many Gen Z are surprisingly very awkward). Please do not attack me for this, it's just my opinion, but a lack of religion leading to a nihilistic viewpoint on life. "The world is gonna end due to "X" in our lives" is very common amongst Gen Z. Social media companies do not value enriching or meaningful content on their platforms, what is popular is defined by an algorithm and that's what's served to millions.
Sleep- Smartphones keeping them up and blue light exposure from being in front of a screen. Everyone talks about how sunlight ages your skin, but what many don't know is visible light ,especially blue light, can also have negative effects on your skin. The sun actually emits red light which has been shown to promote collagen production. Blue light also affects the circadian rhythm of many Gen Z leading to poorer sleep quality.
Of course their are also other environmental possibilities, like air pollution, PFA's , microplastics, and heavy metals.
Plus this study
Thoughts?
Edir: Top comment under post is wong. They claimed there were more Ultra processed foods in the '80s and '90s compared to now, which is blatantly false... drinking less alcohol doesn't mean you're not vaping more or sleeping less or have worse Mental Health or loneliness statistics... food regulations are not strict at all because manufacturers can just introduce ingredients without FDA review, and there's so much out there that really shouldn't be in our food... they also claim they get less UV light so they don't have as much skin damage...? But blue light penetrates deeper and if they're not outside doing stuff that means that they're probably not getting exercise or socializing so....
The comments people upvote is really telling about how people approach this. Stats do not lie.
It's good to be optimistic, but if the world is unhealthier for all of us, why would young people growing up with it fair any better than you did?
The scientific reviewers basically said there just isn’t enough solid human clinical data to show these peptides are safe or effective for the ways people want to use them. Most of them aren’t well characterized chemically(purity, stability, impurities, or how they tend to clump together).
They highlighted a real risk of immune reactions, especially with injectables or nasal forms when compounded, plus general worries about quality control and formulation in a pharmacy setting. They also noted that for some of the conditions being targeted, there are already approved treatments available.
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BPC-157: Only one small, limited human trial for ulcerative colitis, almost no good data on most of the common ways people use it (they were particularly wary of nasal), and the exact mechanism is still pretty unclear. One Human trial by patent holder was never released.
KPV: Very limited human data for the proposed uses or routes; little information on cream or gel formulations.
TB-500: Very limited human data
MOTS-c: Very limited human data
Emideltide/DSIP: Has the longest research history, but the studies are mostly small, old, and inconsistent. Side effects include drops in blood pressure and nausea.
Semax: Mostly relies on animal data, human studies are old and from Russia. Not up to western regulation.
Epitalon: Lacking strong studies for insomnia via the proposed method, plus a theoretical cancer risk tied to how it affects cell growth mechanisms. Telomere extension could allow malignant cells to survive and turn cancerous. Though animal studies actually showed reduced tumor incidence and metastasis.
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Note: These are no longer banned, you can get these peptides compounded at specific pharmacies. However, these peptides are not FDA endorsed nor approved in any way.
The FDA is technically right based on the lack of data. Proceed at your own risk.
More: [FDA panel on peptides will include experts who promote the unproven chemicals favored by RFK Jr.
https://pubs.acs.org/doi/10.1021/acs.jnatprod.4c00977
Notably, (±)-CBL exhibited substantial inhibitory activity on the 5-HT1A receptor, inhibiting the binding of radiolabeled 8-OH-DPAT by an average of 75% at 10 μM and 20% at 1 μM.
Considering that (±)-CBL by itself is a weak agonist of the receptor, this data clearly indicates that (±)-CBL acts as a positive allosteric modulator (PAM) for serotonin.
(Note: CBL has negligible binding at CB1 or CB2)
We observed unexpected results: when coincubated with 40 nM of serotonin, (±)-CBL at a concentration as low as 50 nM significantly enhanced receptor activation with serotonin (Figure 5a). Increasing the dose of (±)-CBL further increased serotonin-induced receptor activation in a dose-dependent manner, reaching over 80% receptor activation when serotonin was incubated with 4 μM of (±)-CBL.
The PAM effect of (±)-CBL was even more pronounced at higher serotonin concentrations. At a low concentration of 5 nM, (±)-CBL significantly enhanced the β-arrestin recruitment of 175 nM serotonin. Co-incubation of 175 nM serotonin and 1 μM (±)-CBL resulted in full activation of the receptor, an effect that neither 175 nM serotonin nor 1 μM (±)-CBL could achieve alone.
Interestingly, when the (±)-CBL concentration was further increased to 12 μM, the PAM effect was diminished. This aligns with the radioligand binding assay (Figure 4), which shows significant competitive binding of (±)-CBL at a 10 μM concentration, suggesting that at very high concentrations, (±)-CBL may hinder serotonin from effectively binding to the active site of the receptor.
However, similar to our previous observations, increasing the (±)-CBL concentration above 10 μM diminished the PAM effect. This reduction is due to the competitive binding of (±)-CBL at high concentrations, which can interfere with the ability of serotonin to effectively bind to the receptor.
This highlights the unique profile of (±)-CBL, a cannabinoid with a distinct allosteric modulatory effect on the 5-HT1A receptor, setting it apart from other phytocannabinoids.
The unique allosteric modulation profile of (±)-CBL at the 5-HT1A receptor underscores its potential as a novel therapeutic agent.
- To end, we have no idea if CBL is biased towards PAMing presynaptic or postsynaptic 5-HT1A, which determines its effect at large. + there are no published mouse pharmacokinetics, no behavioral tests, no in vivo confirmation of the 5-HT₁ₐ PAM effect, and no brain penetration data for CBL specifically.
There is so so many things a substance can do mechanistically, there are also so so many people trying research chems that don't really have more than 3 good mice studies -in which if there's at least 3, we can say ok, several aspects of this chemical have been measured in various ways in mice, which is not humans but still better than nothing.
What if it's silently downregulating something, turning on some genes you don't want, has a metabolite (let's face it, these compounds have tons of metabolites that are varied in action and are harder to measure their impacts unless you do a chronic study, metabolites are already a known thing in psych meds where people's liver enzymes process different ones at different speeds/amounts, leading to varied effects).
For example, popular thc / weed edibles generate more 11-Hydroxy-THC (11-OH-THC) which is generated more in eaten thc as it gets to the gut then the liver, where liver enzymes create it from thc. 11-OH-THC binds to CB1 (your fun main cannabinoid receptors) around 2-3x more potent, and is more water soluble meaning it crosses into the brain easier via the blood brain barrier
Another example could be 9mebc, which has no human testing and is part of the β-Carboline family which go through N-methylation to form β-carbolinium cations which mess with complex 1 functions in mitochondria, generates inflammation from reactive oxidative species (ros) and selectively are attracted to and harm dopamine neurons. While 9mebc has some interesting studies on paper, we don't know its metabolites, and people gloss over its weird UV effects, where UV hits similar chemicals in the 9mebc family and damages dna, in addition to 9mebc being attracted to melanin which are in the substantia nigra (black) dopamine neurons in the brain, and ofc in the skin and this type of damage involves "protonated excited states induce DNA damage via type-I mechanisms (electron transfer), producing oxidized purine residues, single-strand breaks, and cyclobutane pyrimidine dimers. Neutral forms can also transfer triplet energy." - which is basically UV exciting chemicals closely related to 9mebc (in its family), then it steals an electron from a dna base, causing damage. AND it binds with melanin with high affinity and is allegedly retained long term.
>This isn’t to say 9mebc is identical to these compounds, but that it shares a scaffold with documented photochemical and mitochondrial toxicity that rarely gets mentioned in user reports
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https://www.sciencedirect.com/science/article/abs/pii/S1011134414000384
>This is about the 9mebc family, not 9mebc itself, though it raises concerns, good guy...? from a shady family. It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure-activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methyl-harmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet-triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent. https://pubmed.ncbi.nlm.nih.gov/23842892/
>Treatment of astrocyte-depleted cultures with 150-µM 9-me-BC decreased the number of TH + neurons by 50%. Comparatively, the same concentration of 9-me-BC in mesencephalic dopaminergic cultures showed only a slight reduction of dopaminergic neurons. Furthermore, an impaired morphology of TH + neurons was observed in astrocyte-depleted cultures (Fig. 1d), which was considerably improved after treatment with 9-me-BC (Fig. 1e). https://pmc.ncbi.nlm.nih.gov/articles/PMC8592951/
Ok, this wasn't a diss of 9mebc, but its chemical family of β-Carbolines have concerning properties. Harmine is included in this family as well as Pinoline, Harman and Norharman which naturally occur from tryaptamin/tryptophan in which these chemicals are found to be 2-3x higher in parkinson's patients.
Point being, people love to talk about 9mebc when it's really just maoi and some other mysterious understudied mechanisms, the family concerns of toxicity are largely ignored. How about the weird anecdotes of increased tinnitus, or weird head pressure? What's up with that?
How about BPC-157, its only human trial by the patent makers was never published, and in super super rare cases it causes long term anhedonia, and in more minor cases, blunts stimulants/dopamergic substances. Nobody cares if it's "naturally occuring" if you're 100xing it even at the lowest doses, you 100x any trace chemical or peptide in the body and what are you expecting to happen?
Or Dihexa with the rescinded research, misled investors, and odd mechanism that could maybe be pro-tumor. I guess you could include sunifram.unifiram though those are older and barely mentioned these days.
P21, J147, ISRIB which is super sus and has some bad anecdotes...
How about Epitalon which increases teleomeres, but telomeres exist to keep potential cancerous cells from escaping senescence. Why extend telomeres of cells that should have died or cells in the body that are wonky? Epitalon sounds cool, but doesnt disseminate and is probably a bad idea to take, especially if you are older with more damage to your cells/dna over your lifetime.
The same applies to side grades of popular things, just because we know one compound is tested safe in humans, doesn't mean a closely related but untested compound is the same. Would you trust thc over say HHC, THCP, HHCP, etc etc? Think about all these weird prodrugs, sister compounds, even some peptides with no human studies.
Feel free to give your opinions on research chems and their risks that people ignore down below.
>If there's no testing, or barely any online anecdotes (like that's any better), you're taking a risk.
The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.
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interesting thing about DRN > hippocampus projections
selectively reactivates positive experience memories but not neutral or negative
>Given the reported antipsychotic effects of cannabidiol (CBD) and its promiscuous binding at many receptors, we assessed whether CBD could modulate 5-HT2A signalling. Activation of the 5-HT2A intracellular signalling events were assessed using resonance energy transfer- or fluorescence-based biosensors in HEK 293 cells and in rat primary cortical neurons. In 5-HT2A-transfected HEK 293 T cells, CBD antagonized LSD-mediated Gq activation in a saturable way, while leaving β-arrestin2 recruitment unaffected. CBD decreased Gq activation mediated by the 5-HT2A-specific agonist DOI as well as LSD-mediated activity in primary rat neonatal cortical neurons.
>Using Site Identification by Ligand Competitive Saturation (SILCS) simulations, we also predicted that the putative binding site of CBD overlapped with that of oleamide, a positive allosteric modulator of 5-HT2A, and could displace the binding of orthosteric ligands toward the external binding pocket. Based on these findings, we propose that CBD acts as a negative allosteric modulator of 5-HT2A.
