Interestingly, I’ve never heard of Simon Scans, perhaps @DrFraser can elaborate on the perceived value of these more… it seems like a highly profitable private-equity backed venture, but I’m not so familiar with the benefits.
5 Likes
ng0rge
#22
I think consumer health testing is a very profitable growth sector, that’s why I’m surprised that Teal Omics hasn’t launched. But you saw, in the links you posted…
" SimonMed has touted its much lower price point compared to competitors who charge as much as $2,499 for a similar service."
I think it looks good to me.
1 Like
Yes SimonOne is awesome - you’d think I was on commission with them … not.
They have availability in a number of states - we had to go to KY, but it was lovely to visit Louisville.
Getting a look using T3 resolution at everything on your torso is great - also will let you know if atherosclerosis in your aorta - not reliable for cardiac - but vascular disease is a diffuse process usually, so the MRA neck/head that comes with this looks at any vascular disease in these areas, including small vessel disease in your brain.
Overall, if you have the resources - this is a bargain for the information obtained. One has to make sure there is a sensible physician talking you through any abnormalities such that you don’t investigate things that are unlikely to be significant. You also get to track hippocampal volume which is predictive of dementia.
SimonOne Whole Body MRI Plus
Recommend the Whole Body Plus $1250 in most situations. Call 877.653.3558 to schedule. Information on their website is here. :
Go here to see a sample report.
Note the Neuroquant testing and imaging on the brain and percentiles by age/gender.
8 Likes
RobTuck
#24
I posted the criteria at the top and discussed them briefly. This is the link to the full article.
https://esmed.org/MRA/mra/article/view/5138/99193547794
According to Nir Barzilai, we need clinical trials, not case reports, and he doesn’t count rapamycin:
adssx
#26
It’s just the top four from this ranking: Updated Prioritization of Geroscience-Guided FDA-Approved Drugs Repurposed to Target Aging - the most interesting findings in February 2024 Medical Research Archives?
Namely, SGLT2i, metformin, bisphosphonates, and GLP-1RAs.
Rapamycin is ranked right after those but he did not list it due to this criterion “Be tested for safety and efficacy on hundreds, possibly thousands of people in clinical trials”.
Sorry, didn’t see this. Can we lock this thread?
adssx
#28
I merged the threads, it’s still interesting that in mainstream media he limits his recommendation to the top 4. And I think it makes sense.
3 Likes
Bisphosphonates
I’ve had two bone docs say to be very careful with Bisphosphonates. I wouldn’t take it without bone related desperation
1 Like
LaraPo
#30
Metformin effects in Non-diabetic patients:
Metformin, traditionally used for diabetes management, has shown several interesting effects in non-diabetic patients:
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Weight Loss: Metformin can aid in weight management by reducing appetite, leading to modest but clinically significant weight loss².
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Cardiovascular Benefits: There is evidence suggesting that metformin may have cardioprotective effects, potentially reducing the risk of cardiovascular events¹.
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Insulin Sensitivity: It can improve insulin sensitivity, which is beneficial for individuals with insulin resistance³.
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Anti-inflammatory Effects: Metformin has been noted to reduce inflammation, which can be beneficial for various conditions³.
However, it’s important to note that more research is needed to fully understand the long-term effects and safety of metformin in non-diabetic individuals⁴.
Source: Conversation with Copilot, 10/30/2024
(1) Should I consider metformin therapy for weight loss in patients with … Should I consider metformin therapy for weight loss in patients with obesity but without diabetes? | Cleveland Clinic Journal of Medicine.
(2) Metformin in patients with and without diabetes: a paradigm shift in … https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0860-y.
(3) What Happens if You Take Metformin and Don’t Have Diabetes: A Guide. https://caregiversupportnetwork.org/other-age-related-conditions/diabetes-management/what-happens-if-i-take-metformin-and-i-dont-have-diabetes/.
(4) What Happens If A Non Diabetic Takes Metformin - Statcare. What Happens If A Non Diabetic Takes Metformin - Statcare.
(5) New benefits from anti-diabetic drug metformin - ScienceDaily. New benefits from anti-diabetic drug metformin | ScienceDaily.
1 Like
RobTuck
#31
In my experience, metformin’s contribution to reducing inflammation falls off sharply if the baseline level is already low. One calculation is that it might reduce a CRP of 0.5 down to 0.45, which is within measurement error and normal variation.
The following represents the consensus of metformin’s contributions to longevity among my AI systems.
Metformin’s potential role as a longevity agent is supported by both mechanistic insights and clinical evidence, especially in metabolic disease and aging research. The following mechanisms are central to metformin’s purported longevity effects, each rooted in its interactions with cellular pathways that affect aging, inflammation, and metabolic health.
1. AMPK Activation and Metabolic Regulation
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Mechanism: Metformin activates AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. AMPK senses low energy (high AMPratio) and shifts cellular metabolism toward energy conservation and repair processes, such as increased glucose uptake, mitochondrial biogenesis, and lipid oxidation.
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Longevity Implications: AMPK activation reduces anabolic (growth) processes associated with cellular senescence and supports catabolic processes that help clear damaged cellular components. AMPK activation is linked to improved metabolic function, reduced insulin resistance, and potential reductions in age-related diseases.
2. Reduction of Oxidative Stress and ROS Accumulation
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Mechanism: Metformin mildly inhibits complex I of the mitochondrial electron transport chain, reducing ATP production. This inhibition can decrease the production of reactive oxygen species (ROS) in a dose-dependent manner.
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Longevity Implications: Lower ROS levels help mitigate oxidative damage, which is a major contributor to cellular aging and DNA damage. This anti-oxidative effect, especially in cells with high metabolic rates, can help reduce chronic inflammation and delay age-related degenerative changes.
3. Reduction of Systemic Inflammation
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Mechanism: Metformin decreases circulating levels of pro-inflammatory cytokines, such as TNF-α, IL-6, and CRP, by reducing ROS and by modulating NF-κB signaling—a key regulator of inflammation.
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Longevity Implications: Chronic inflammation (often termed “inflammaging”) accelerates aging processes and contributes to age-related diseases like atherosclerosis, Alzheimer’s disease, and cancer. By reducing systemic inflammation, metformin may protect against these diseases and support cellular integrity over time.
4. Modulation of Insulin/IGF-1 Signaling Pathway
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Mechanism: Metformin enhances insulin sensitivity and reduces hyperinsulinemia. It lowers levels of insulin-like growth factor 1 (IGF-1) in certain tissues by improving insulin signaling, especially in insulin-resistant individuals.
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Longevity Implications: Insulin and IGF-1 signaling pathways are closely linked to cellular growth and proliferation. Lower levels of these growth signals are associated with increased lifespan in animal models and may reduce risks of cancer and other growth-related disorders in humans, as high IGF-1 levels are often linked to accelerated aging.
5. Influence on Cellular Senescence and SASP (Senescence-Associated Secretory Phenotype)
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Mechanism: Metformin reduces the SASP, a pro-inflammatory and pro-tumorigenic secretory profile that senescent cells adopt. Through AMPK activation and mitochondrial regulation, metformin can limit SASP factors like IL-1, IL-6, and MMPs, which drive local and systemic inflammation.
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Longevity Implications: By mitigating the SASP, metformin reduces the spread of senescence signals to neighboring cells, thereby slowing the accumulation of senescent cells—a hallmark of aging. This can help preserve tissue function and reduce the systemic inflammatory load associated with cellular aging.
6. Autophagy Stimulation
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Mechanism: AMPK activation also induces autophagy, a cellular housekeeping process where damaged proteins and organelles are degraded and recycled. Autophagy is essential for cellular maintenance and stress response.
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Longevity Implications: Enhanced autophagy is associated with increased lifespan in many model organisms. By promoting autophagy, metformin supports the removal of dysfunctional cellular components, which can delay degenerative processes associated with aging.
7. Epigenetic Modulation and DNA Damage Protection
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Mechanism: Metformin has been shown to modulate the expression of various longevity-related genes by affecting epigenetic factors such as histone acetylation and methylation. Additionally, its reduction in oxidative stress may help decrease DNA damage.
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Longevity Implications: Epigenetic modifications and DNA integrity are crucial for healthy aging. By modulating gene expression and preserving DNA structure, metformin may contribute to cellular stability over time and potentially extend lifespan.
8. Gut Microbiome Modulation
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Mechanism: Metformin alters the composition of the gut microbiota, favoring bacteria associated with improved glucose and lipid metabolism. For instance, metformin increases levels of short-chain fatty acid (SCFA) producers, which are beneficial for metabolic health.
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Longevity Implications: The gut microbiome plays a role in inflammation, metabolism, and immune function. By promoting a healthy gut microbiome, metformin may indirectly enhance immune function, reduce inflammation, and improve metabolic health—all contributing to longevity.
Clinical Evidence
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Diabetes and Mortality Studies: Studies like the UKPDS and others have shown that metformin not only improves glycemic control in diabetes but is also associated with lower all-cause mortality, independent of glycemic control. This suggests that its benefits extend beyond blood sugar regulation.
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TAME Trial (Targeting Aging with Metformin): The ongoing TAME trial is designed to assess metformin’s effects on age-related diseases, aiming to establish it as a geroprotector. Early observational data and retrospective studies already suggest metformin users experience fewer age-related diseases.
Summary
Metformin’s longevity effects appear to stem from a multifaceted approach to cellular and systemic regulation, targeting key pathways involved in energy metabolism, inflammation, cellular maintenance, and genomic stability. While metformin’s exact effect on human lifespan remains under investigation, the convergence of mechanistic and clinical data indicates it has broad potential as a longevity-promoting agent.
Its influence on AMPK, autophagy, inflammation, and the gut microbiome aligns with pathways known to impact lifespan in multiple organisms, suggesting metformin could be a valuable tool in age-related health maintenance, especially for individuals with metabolic dysregulation or at risk of age-related inflammatory diseases.
4 Likes
adssx
#32
