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== Metformin and Longevity ==

Metformin, a drug primarily used to treat type 2 diabetes, has attracted considerable interest for its potential effects on longevity and aging-related diseases. It is believed to impact aging through several pathways, notably through its effects on metabolic and cellular processes implicated in the aging process.

=== Background ===
Metformin was first synthesized in the 1920s and has been used since the 1950s to manage hyperglycemia in individuals with type 2 diabetes due to its ability to decrease hepatic glucose production and improve insulin sensitivity ([[doi:10.2337/dc16-1503]]).

=== Mechanism of Action ===
Metformin's anti-aging effects are believed to stem from its ability to activate AMP-activated protein kinase (AMPK), a cellular energy sensor and regulator that plays a critical role in maintaining energy homeostasis ([[doi:10.1016/j.cmet.2011.07.005]]). Activation of AMPK can impact several cellular and metabolic processes associated with aging, including inflammation, oxidative stress, and autophagy. By modulating these processes, metformin could potentially delay aging and extend lifespan.

=== Potential Benefits ===
Metformin’s potential longevity benefits are supported by several studies. Research suggests that it may reduce the incidence of age-related conditions like cardiovascular disease, cancer, and cognitive decline, potentially contributing to an increased lifespan ([[doi:10.1111/acel.13028]]).

==== Cardiovascular Health ====
Metformin is suggested to have cardioprotective effects, potentially reducing the risk of cardiovascular diseases and events in non-diabetic populations. These effects may be due to its role in improving lipid profiles, reducing inflammation, and improving endothelial function ([[doi:10.1093/eurheartj/ehw233]]).

==== Cancer Prevention ====
Several studies have pointed towards the possible anti-cancer properties of metformin, which may be attributed to its ability to lower circulating insulin levels and inhibit the mTOR pathway, a signaling pathway associated with cell growth and proliferation ([[doi:10.1158/1078-0432.CCR-13-0667]]).

==== Cognitive Health ====
Metformin has shown potential in reducing the risk of cognitive decline and neurodegenerative diseases like Alzheimer’s, possibly due to its anti-inflammatory and anti-oxidative properties, along with its ability to enhance brain insulin sensitivity ([[doi:10.1016/j.neurobiolaging.2011.12.013]]).

=== Considerations for Longevity Seekers ===
Individuals seeking to use metformin as a longevity-enhancing agent should weigh the potential benefits against the possible risks. While it has shown promise in extending healthspan, the overall impact on lifespan in non-diabetic populations is still under investigation, and long-term usage could have unforeseen consequences.

==== Risk and Side Effects ====
While metformin is generally well tolerated, it does come with potential side effects and risks. Common side effects include gastrointestinal distress, such as nausea, vomiting, and diarrhea ([[doi:10.1111/dom.13429]]). Additionally, there is a rare but serious risk of lactic acidosis, particularly in individuals with impaired kidney function ([[doi:10.1001/jama.2016.0236]]).

==== Dosing and Administration ====
For those considering metformin for longevity, it is crucial to consult a healthcare provider for appropriate dosing and to discuss potential interactions with other medications or underlying health conditions. The dosage may vary, but it typically ranges from 500mg to 2550mg per day for type 2 diabetes treatment. However, the optimal dose for longevity purposes is not well established and requires careful consideration and monitoring.

=== Clinical Studies and Trials ===
Several clinical trials and studies are exploring the effects of metformin on lifespan and aging-related conditions. The Targeting Aging with Metformin (TAME) trial is a notable example, aiming to assess metformin's ability to extend healthspan and reduce the incidence of age-related diseases ([[doi:10.18632/aging.101647]]).

==== TAME Trial ====
The TAME trial is designed to evaluate whether metformin can delay the onset of age-related diseases and conditions, such as cancer, cardiovascular disease, and Alzheimer's, in an aging population. The outcomes of this trial could potentially influence the repurposing of metformin as an anti-aging intervention, impacting regulatory and clinical practices in gerontology and geriatrics.

=== Conclusion ===
Metformin, a well-established diabetes medication, has shown promising potential as a longevity-enhancing drug due to its multifaceted impact on cellular and metabolic processes related to aging. While preliminary findings suggest benefits in reducing age-related conditions and possibly extending lifespan, further research, including ongoing clinical trials like TAME, is crucial to fully understand its efficacy and safety in non-diabetic populations seeking longevity benefits.