💊 Metformin – Longevity Applications
What is metformin and why is it considered a longevity drug?
Metformin is a diabetes medication that may extend lifespan by improving insulin sensitivity and mitochondrial health.
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Does metformin reduce biological aging?
Some evidence suggests it may slow epigenetic aging and protect against age-related diseases.
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How does metformin affect insulin and glucose?
It lowers glucose production in the liver and increases insulin sensitivity in tissues.
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Can healthy people take metformin for longevity?
Some biohackers do, but research is ongoing and off-label use requires medical supervision.
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Does metformin interfere with exercise benefits?
Yes, it may blunt muscle adaptation to resistance training in some people.
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What are the common side effects of metformin?
Gastrointestinal upset, B12 deficiency, and rare lactic acidosis in susceptible individuals.
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Does metformin improve mitochondrial function?
Paradoxically, it mildly inhibits mitochondrial complex I, which may trigger beneficial stress responses.
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Is metformin anti-inflammatory?
Yes, it reduces markers like CRP and TNF-alpha, supporting healthy aging pathways.
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Can metformin lower cancer risk?
Several observational studies link metformin use to reduced risk of various cancers.
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Does metformin affect fertility or hormones?
It can support hormonal balance in PCOS but may lower testosterone in men with long-term use.
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How does metformin compare to rapamycin?
Metformin targets metabolism and insulin pathways; rapamycin affects mTOR — they may be synergistic.
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What’s the optimal dose of metformin for longevity?
Doses vary — often 500–1000 mg/day is used off-label, with minimal effective dose preferred.
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Should metformin be cycled or taken continuously?
Some suggest cycling to avoid exercise interference and preserve metabolic flexibility.
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Is metformin being studied for aging?
Yes, the TAME trial (Targeting Aging with Metformin) is investigating its effects on lifespan and healthspan.
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Can metformin be combined with NAD+ boosters?
Yes, many longevity protocols use both for mitochondrial and metabolic support.
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Does metformin cause B12 deficiency?
Yes, with long-term use. Regular monitoring and supplementation are recommended.
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Can metformin improve brain health?
Possibly — it may enhance neurogenesis and reduce risk of cognitive decline.
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How soon do metformin benefits appear?
Metabolic effects often begin within weeks; long-term aging benefits are gradual.
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Is metformin safe for non-diabetics?
Generally well tolerated in healthy people, but it’s a prescription drug requiring supervision.
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🧬 Rapamycin – mTOR Inhibition & Lifespan Extension
What is rapamycin and how does it affect aging?
Rapamycin inhibits mTOR, a nutrient-sensing pathway linked to aging, promoting autophagy and cellular repair.
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Is rapamycin FDA-approved for longevity?
No, it’s approved for transplant immunosuppression; longevity use is off-label and experimental.
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How does rapamycin differ from metformin?
Rapamycin targets mTOR, while metformin affects AMPK and insulin pathways. They may be synergistic.
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Can rapamycin increase lifespan in humans?
Animal studies show lifespan extension; human trials are ongoing (e.g., PEARL trial).
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What is the optimal dose of rapamycin for longevity?
There’s no consensus. Low weekly dosing (e.g., 5–10 mg) is common in longevity circles.
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Should rapamycin be taken daily or weekly?
Weekly dosing is preferred to reduce immunosuppression while maintaining anti-aging effects.
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Does rapamycin cause immunosuppression?
At transplant doses, yes. At low intermittent doses, it may boost immune surveillance in aging.
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What are the potential side effects of rapamycin?
Mouth sores, elevated lipids, insulin resistance, or wound healing delay in some individuals.
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Is rapamycin safe for healthy adults?
Long-term safety in healthy people is not yet fully established — supervision is advised.
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Does rapamycin improve cognitive function?
Animal studies suggest benefits in memory and neuroprotection; human data is limited.
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Can rapamycin reduce cancer risk?
It may suppress tumor growth and is being investigated for cancer prevention and treatment.
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Does rapamycin affect blood sugar levels?
It can impair glucose tolerance in some users; combining with exercise or metformin may offset this.
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Is rapamycin legal to use for aging?
It’s legal by prescription but not approved for anti-aging — considered off-label use.
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What are alternatives to rapamycin?
Fasting, exercise, and compounds like berberine or spermidine also impact mTOR/AMPK balance.
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Can rapamycin extend healthspan without side effects?
Intermittent dosing shows promise in animals, but human trials will confirm safe protocols.
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Is topical rapamycin used for skin aging?
Yes, early studies suggest it may reduce signs of skin aging and senescent cell burden.
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What is the PEARL trial?
A clinical trial investigating rapamycin’s effect on aging biomarkers in healthy older adults.
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Does rapamycin interact with other longevity drugs?
Potentially. Combinations with metformin, NAD+ boosters, and statins should be monitored.
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How is rapamycin obtained for longevity use?
Via prescription (e.g., Sirolimus), usually from physicians specializing in preventative or anti-aging medicine.
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💢 Statins & Longevity – Controversies and Evidence
What are statins and how do they work?
Statins lower LDL cholesterol by inhibiting HMG-CoA reductase, a key enzyme in cholesterol synthesis.
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Do statins improve lifespan?
They reduce cardiovascular mortality, but their benefit in primary prevention for longevity is debated.
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Are statins overprescribed?
Some experts argue they are, especially in people without cardiovascular disease.
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Can statins cause side effects?
Yes — including muscle pain, fatigue, liver enzyme elevations, and rarely cognitive changes.
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Do statins reduce inflammation?
Yes, they lower CRP and other inflammatory markers, which may contribute to their benefit.
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Do statins increase risk of diabetes?
Slightly, especially in people already at risk, due to effects on glucose metabolism.
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Can statins affect cognition?
Rarely, some users report brain fog or memory issues; most large trials show minimal cognitive effect.
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Should everyone over 50 take statins?
Not necessarily — benefit depends on risk factors, biomarkers, and individual goals.
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Are there alternatives to statins for longevity?
Yes — lifestyle, omega-3s, red yeast rice, berberine, and PCSK9 inhibitors in some cases.
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How do statins compare to exercise for cardiovascular health?
Both reduce mortality — but exercise improves broader health domains including cognition and mobility.
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Can statins reduce biological age?
Possibly through reduction in systemic inflammation and vascular aging.
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What is the role of LDL in aging?
Elevated LDL is linked to cardiovascular disease; its role in healthy aging remains debated.
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Do statins affect mitochondria?
Some evidence suggests statins may impair CoQ10 and energy production in sensitive individuals.
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Should statins be taken at night?
Yes — especially short-acting statins like simvastatin, due to nighttime cholesterol synthesis.
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Can CoQ10 reduce statin side effects?
Supplementing CoQ10 may help alleviate muscle-related side effects in some users.
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How are statins monitored?
Via blood lipid panels, liver enzymes, CK (for muscle damage), and patient-reported symptoms.
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Are statins useful in non-cardiac longevity strategies?
Possibly, due to their anti-inflammatory effects — but personalized risk-benefit analysis is key.
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Can statins affect exercise performance?
Some users report reduced endurance or muscle strength — though not consistently observed.
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Should statins be paused in old age?
Deprescribing may be appropriate in frail elderly or those with limited life expectancy — consult with a geriatrician.
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🫀 ACE Inhibitors & Cardiovascular Protection
What are ACE inhibitors and how do they work?
They block angiotensin-converting enzyme, lowering blood pressure and reducing cardiovascular strain.
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Can ACE inhibitors promote longevity?
Some studies link ACE inhibitors with reduced mortality and improved cardiovascular aging.
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Are ACE inhibitors better than ARBs for aging?
Both protect the heart and kidneys; some studies favor ACE inhibitors for heart failure, others ARBs for side effect profile.
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How do ACE inhibitors affect blood vessels?
They improve endothelial function, reduce arterial stiffness, and lower oxidative stress.
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Can they help prevent heart attacks or strokes?
Yes — especially in high-risk individuals or those with hypertension or diabetes.
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Are ACE inhibitors used in people without hypertension?
Sometimes — in those with heart failure, kidney disease, or elevated vascular risk.
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What are common side effects?
Cough, low blood pressure, dizziness, kidney function changes, or increased potassium.
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Do ACE inhibitors protect kidney function?
Yes — they reduce intraglomerular pressure and are standard in diabetic nephropathy.
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How are ACE inhibitors monitored?
Blood pressure, electrolytes (especially potassium), and kidney function (creatinine, eGFR).
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Do they affect cognitive aging?
Some studies suggest better brain perfusion and reduced dementia risk vs. other antihypertensives.
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🧪 Experimental Longevity Compounds & Senolytics
What are senolytics?
Senolytics are compounds that selectively remove senescent cells, which contribute to aging and chronic disease.
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What is FOXO4-DRI and how does it work?
FOXO4-DRI is a peptide that disrupts survival signaling in senescent cells, inducing apoptosis in dysfunctional cells.
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Are senolytics proven to extend lifespan?
In mice, yes. Human trials are still early, but promising for healthspan improvements.
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What are some natural senolytics?
Fisetin, quercetin, piperlongumine, and EGCG have senolytic properties in preclinical studies.
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How are senescent cells detected?
Biomarkers like p16INK4a, SASP factors, and imaging are used in research; no routine clinical test yet.
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What is the optimal dosing frequency for senolytics?
Intermittent "hit and run" dosing (e.g. monthly or quarterly) is used to minimize side effects.
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What are potential side effects of senolytics?
Unknown in long term; some compounds may affect platelet function or cause transient fatigue.
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Are any senolytic drugs in clinical trials?
Yes — UNITY's UBX1325, and Mayo Clinic–backed trials using Dasatinib + Quercetin.
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Is fisetin effective as a senolytic?
In mice, yes. Human trials are ongoing to confirm safety and efficacy in aging-related diseases.
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Can senolytics be combined with other longevity drugs?
Yes, combinations with rapamycin, metformin, and NAD+ boosters are being explored for synergy.
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