r/immortalists

It is difficult to describe in a few words the anti-aging properties of broccoli. It is a blessed vegetable that contains a wide variety of antioxidant substances. A particularly powerful antioxidant substance is sulforaphane (or thioraphane), which was discovered by researchers at Johns Hopkins University. When this broccoli component was administered to laboratory animals, it resulted in an increase in the activity of the enzymes involved in the detoxification system of the animals and a two-thirds reduction in the cancer rate. Broccoli contains many antioxidant substances that fight free radicals, such as vitamin C, beta-carotene, valanone, indoles, glutathione, and lutein. Broccoli is also one of the richest sources of chromium, a trace mineral known to contribute to the prolongation of life and protection against the woes caused by unregulated insulin and high blood sugar levels. In women, broccoli helps the body eliminate harmful estrogens that promote the development of cancer. Additionally, those who consume broccoli have lower rates of colon and lung cancer, as well as lower rates of cardiovascular disease. The consumption of broccoli has even been associated with extending the survival time of patients suffering from lung cancer.

Best scientific papers:

1. This review highlights broccoli's rich nutritional profile (fiber, vitamins A, C, K, minerals) and bioactive compounds (glucosinolates, sulforaphane, indole-3-carbinol) that possess antioxidant, anti-inflammatory, and anticancer effects, supporting multiple health mechanisms relevant to longevity. https://www.mdpi.com/2079-6382/12/7/1157

2. This deep dive into glucosinolates, phenolic compounds, and antimicrobial peptides in broccoli emphasizes compounds like sulforaphane (from glucosinolates), which are of interest for anti-aging and organ health as they trigger detox/repair pathways (e.g., Nrf2). https://www.mdpi.com/1420-3049/30/11/2262

3. An overview suggesting broccoli may reduce the risk of certain cancers via glucosinolate-derived products (isothiocyanates, indoles) but also raises a minor caution about possible genotoxic effects in some experimental models, indicating that processing and moderate intake are key. https://pubmed.ncbi.nlm.nih.gov/21906651/

4. This study examines how processing impacts beneficial compounds, finding that steaming tends to preserve more beneficial compounds (polyphenols, glucosinolates, sulforaphane) than boiling, while raw consumption may offer the highest sulforaphane but could be harder to digest for some individuals. https://www.researchgate.net/publication/233751142_An_overview_of_health-promoting_compounds_of_broccoli_Brassica_oleracea_var_italica_and_the_effect_of_processing

5. A large prospective cohort study in U.S. adults found that consuming broccoli 1–2 times per week was associated with a 32–43% lower all-cause mortality risk, as well as lower cardiovascular and cancer mortality risks, providing strong epidemiologic support for regular intake. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1286658/full

6. An animal study showed that introducing broccoli by-product flour into the diet of mice on a high-fat diet reduced adiposity (body fat) and enhanced antioxidant enzyme activity (SOD, glutathione S-transferase), suggesting benefits for metabolic health and mitigating obesity/metabolic stress. https://www.researchgate.net/publication/363355001_Beneficial_Effects_of_Broccoli_Brassica_oleracea_var_italica_By-products_in_Diet-induced_Obese_Mice

This review looks at what we keep seeing (Ozempic face) and investigates whether it's a result of rapid fat loss or could GLP-1 rector agonists directly accelerate aging. The authors actually conclude that both may be true. And ironically, they also have research showing they have anti-aging effects on other parts of the body by reducing inflammation and oxidative stress. They examine whether mechanisms beyond fat loss may contribute to skin aging during GLP-1 therapy. Skin aging is characterized by reduced mitotic activity, impaired skin barrier function, decreased collagen and elastin product, diminished cellular proliferation, increased apoptosis, and elevated oxidative stress. Increased production of reactive oxygen stress damages DNA and cellular membranes, activates signaling pathways that reduce pro collagen synthesis, and stimulates inflammatory pathways involved in collagen metabolism.

GLP-1s have proven research on type 2 diabetes, obesity, and weight loss, but they also have demonstrated anti-inflammatory effects have been investigated for skin diseases. As their use has increased, so has facial aging associated with significant weight loss been noticed. The change is usually connected to the loss of facial fat because it alters facial contours and results in excess skin, more visible wrinkles, and changes in facial proportions. The authors note that this phenomenon is not unique to GLP-1s though, and has also been described following bariatric surgery. Histological studies of patients with major weight loss have demonstrated alterations in dermal structure, including changes in collagen and elastic fiber density.

The authors describe evidence suggesting that GLP-1s may influence dermal white adipose tissue (DWAT) and adipose-derived stem cells (ADSCs). These both express GLP-1 receptors. DWAT contribute to skin maintenance and regeneration and reduced DWAT has been associated with aging skin, decreased collagen production, and increased activity of an enzyme involved in collagen degradation (matrix metalloproteinase-1.) Studies show that GLP-1 receptors on ASDCs may decrease the production of protective cytokines and growth factors, impair fibroblast migration and collagen synthesis, and increase oxidative stress within the cells. There's also a lot more interesting in the weeds findings, but don't want this to get crazy long. They touch on estrogen receptors, muscle loss, etc.

The authors ALSO found evidence suggesting that GLP-1RAs may have effects that support skin health too. It reduces chronic inflammation and lower concentrations of AGEs. They also associate this with reduction of blood glucose levels. There are various studies touching on this as well. The authors also found from other studies that GLP-1s improve endothelial function and increase microvascular perfusion within the skin and subcutaneous tissue. But they note that no published study has directly linked these effects to delay skin aging yet and state additional research is needed.

The point of this review is that it argues Ozempic face is way more complex than simply losing facial fat, but there is currently still not enough evidence that GLP-1s directly age the skin. Please do not take this as discouragement from using them or as fear mongering. I want people to know the science of what could be going on. Keep in mind that this is a mini review, not a clinical trial. A lot of the mechanisms come from biology research and inferences. But what I would offer from this is. If these mechanisms are happening and you are using them, what would theoretically protect against them? If you're worried about reduced collagen signaling, you would want things that support collagen production. If you're concerned on oxidative stress, you would want to reduce oxidative damage. If it's about the reduced stem cell activity, you want to support tissue repair and regeneration. If you're worried about the loss of dermal estrogen signaling, that is currently being studied in peri and postmenopausal research. This paper to me actually is something that can be used on future research on how to combat these things.

Paschou IA, Sali E, Paschou SA, Tsamis KI, Peppa M, Psaltopoulou T, Nicolaidou E, Stratigos AJ. GLP-1RA and the possible skin aging. Endocrine. 2025 Sep;89(3):680-685. doi: 10.1007/s12020-025-04293-w. Epub 2025 Jun 11. PMID: 40498168; PMCID: PMC12370548.

https://www.dropbox.com/scl/fi/xldxphuzqw86m7xqx5s20/GLP-1RA-and-the-possible-skin-aging.pdf?rlkey=iiqiobjnckzwu3zt4yqxm1djl&st=pato0lja&dl=0 (dropbox link is actually from Thriving Through Menopause by Chiza Westcarr)

Over the past few years we've seen a lot of interesting longevity research. Most of it isn't about living to 150 or reversing aging overnight. Instead, it's made up of small steps that slowly move the field forward.

One study that really caught my attention looked at something surprisingly simple: omega-3, vitamin D and regular exercise.

Researchers followed 777 older adults for three years. They measured biological aging using epigenetic clocks, which estimate biological age based on DNA methylation rather than your birth date.

The results weren't dramatic, but they were real.

People taking omega-3 showed a small slowing of biological aging, and the combination of omega-3, vitamin D and exercise appeared to produce an even greater effect. Depending on the epigenetic clock used, the difference was roughly equivalent to slowing biological aging by about 3 to 4 months over the course of three years.

That probably won't make headlines.

But maybe that's exactly why it's important.

Not every breakthrough in longevity will look like a miracle. Sometimes progress comes from small improvements that are measurable, repeatable and tested in real people.

There are several other studies and technologies I'd love to discuss next, including:

• ER-100 and the first human cellular reprogramming trial.
• Senolytics and the idea of removing senescent cells.
• AI helping design therapies for aging.
• Epigenetic clocks and how we actually measure biological age.

Which one would you want to dive into next?

(Updated to add this note: This study is on repigmentation and grey hair research, I realize the title is blind)

Sharing a study looking at repigmentation. That and hair treatments, hair follicle stimulation, and hair follicle microenvironments seem to be a common interest.

Melanocyte stem cells (McSCs) regenerate the pigment producing melanocytes that color hair during each hair cycle. As these stem cells become depleted or stop contributing to hair regeneration, hair gradually loses pigment and turns grey. Understanding why this stem cell population fails has been a long standing question in stem cell biology. The prevailing model proposed that McSCs remain undifferentiated within a specific region of the hair follicle called the bulge, while the cells they produce leave this region, become mature melanocytes, and never return to the stem cell population.

Background info that might help: Stem cells can either maintain their identity or begin differentiating. Differentiation is the process by which a stem cell gradually acquires the structure and function of a specialized cell. In the traditional model, this process moves in one direction. Once a stem cell begins differentiating, it is expected to continue towards becoming a mature cell and permanently lose the ability to function as a stem cell. This study asks whether melanocyte stem cells instead retain the ability to reverse this process.

Back to the paper. The authors found that melanocyte stem cells do not always follow a one way path toward differentiation. During each hair growth cycle, many melanocyte stem cells begin expressing genes associated with mature melanocytes and enter an intermediate stage of differentiation. Rather than continuing directly to become mature pigment producing cells, some later lose these differentiation markers and regain the characteristics and function of melanocyte stem cells. The authors conclude that this revertsal, called differentiation, is a normal mechanism used to maintain the melanocyte stem cell population.

The authors first examined where McSCs are located before hair growth begins. Previous studies suggested that these cells are primarily found in the bulge. However, 3d imaging showed that most McSCs are actually located in the neighboring hair germ. By tracking individual cells over time, the authors showed that McSCs in their hair germ both generated mature melanocytes and produced cells that remained in the stem cell population for future hair cycles. This demonstrated that the hair germ contains the main population responsible for both pigment regeneration and long term maintenance. The authors then ask whether McSCs change ad hair growth begins. They found that these cells changed shape and activated genes involved in pigment production before producing mature melanocytes. Single cell RNA sequencing confirmed that the cells occupied an intermediate molecular state between undifferentiated melanocyte stem cells and fully differentiated melanocytes. These changes occurred early in regeneration, showing that McSCs normally begin the differentiation process during each hair cycle.

To determine whether differentiating cells could return to the stem cell population, the actors permanently labeled McSCs expressing Oca2, a one that is activated late during differentiation. As expected, some of these labeled cells became mature melanocytes that produced pigment in the hair bulb. Unexpectedly, other labeled cells migrated to another region of the hair follicle, switched off pigmentation genes, and persisted as McSCs through multiple rounds of hair regeneration. This demonstrated that cells that had already progressed well into differentiation could reverse that process and regain stem cell function.

The authors showed that nearly all melanocyte stem cells can undergo reversible differentiation rather than maintaining a permanently undifferentiated population. This process is controlled by local signals within the hair follicle. WNT signaling promotes differentiation in the hair germ, whereas reduced WNT signaling in the bulge allows cells to dedifferentiate and regain stem cell function. During aging, many McSCs fail to return to the hair germ and instead remain in the bulge, reducing melanocyte regeneration and contributing to hair greying.

I find it odd that the study doesn't investigate why. Like okay it explains where the cells get stuck... but then doesn't go for more. So like several possibilities could be the cause. The ECM around the follicle stiffens with age, adhesion molecules change, epithelial cells stop producing guidance cues, McSCs themselves lose the migration capacity, or all of these things happen together. It's hard to actually figure out what the best intervention is without that being identified. I'll set aside that a successful repigmentation study does exist and come back to that in the comments so I can just separate ideas. But, restoring McSC movement is something to think about. If those cells are stranded in the bulge and still alive, but just in the wrong place, a treatment that would encourage them to migrate back into the hair germ before the next cycle could be a plan of attack. So manipulating cell adhesion molecules (how tightly cells stick to their surroundings), extracellular proteins, chemokine signaling (cellular communication that guide movement), cytoskeletal regulators (proteins that control the assembly, disassembly, and organization of a cell's structural network) that control migration, etc because these would restore the normal regenerative cycle not trying to force pigment production. The paper shows that McSC identity depends on local signals so another approach could be instead of targeting the stem cells directly, you could try restoring the signals of the aging hair germ (WNT signaling, TGF-β , endothelin, stem cell factor/c-Kit, or notch signaling. Navigating this seems easier said than done though as these pathways regulate many cell types so it would need really precise timing. Also grey hair has been difficult to reverse by changing one of these pathways alone is prob not likely to restore the normal regenerative cycle and this paper kind of reinforces that. Another treatment approach could be if you think about how some McSCs become stuck in a partially differentiated state, it may be possible to push them back toward a differentiated state. The difficult is that forcing cells backwards carries risks if control is lost (abnormal growth or cancer). A different approach to look at would be instead of reversing greying, preserve the normal cycle earlier in life. If the problem is that stem cells gradually lose mobility over decades, then maintaining extracellular matrix structure, preventing fibrosis, or reducing chronic inflammation around the follicle might delay greying. If you are actually interested in these topics and looking through them, these are all 3 common themes we keep seeing across all literature right now in various spaces btw, if you're new here and interested write those down lol. And then a possible treatment could be if you think how McSCs only regenerate pigment during the normal hair cycle, a treatment or therapy might work if it times up with several events. So you'd want to trigger a new hair cycle, restore the proper niche signals, allow stem cells to migrate, and then let pigment producing melanocytes regenerate naturally. But that's very complex.

>

Abstract

>For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations, which leads to hair greying in most humans and mice. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

>Supplementary information The online version contains supplementary material available at: https://doi.org/10.1038/s41586-023-05960-6.

>Peer review information Nature thanks Nick Barker, Rui Yi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Cheung N (June 30, 2026) Focal Polycomb-Mediated Repression of Neuronal Identity and Synaptic Maintenance Genes in Aging Neurons. Cureus 18(6): e111824. doi.org/10.7759/cureus.111824

Good vid here. Business Insider covers aging and the supposed max age humans can live. It’s interesting that Business Insider continues to focus on aging, and emergent technologies that may extend life.

"Today, more people are living past 100 than ever before — even though the maximum human lifespan hasn't moved past 115 years. But is that about to change? The Limit host Daniel T. Allen spent months talking to medical researchers, biohackers, and centenarians. He also went through a battery of tests worth over $12,000 at a longevity clinic to find out how long he might live. In this episode, Business Insider looked into what could radically extend human lifespan, including FDA-approved drugs, cellular reprogramming, and Bryan Johnson's $2 million "Don't Die" protocol."

https://www.youtube.com/watch?v=WKi9FHrGAjA