Longevity Pharmacology: What the ITP, TAME Trial, and Senolytic Research Really Show

The idea that aging itself could be treated as a medical condition — not just its downstream diseases, but the fundamental biological processes driving cellular decline — has moved from fringe speculation to mainstream geroscience in less than a decade. The evidence driving this shift is not anecdote or theoretical: it is controlled laboratory data from the most rigorous preclinical aging research program ever conducted, combined with surprising findings in large human cohorts and a growing body of early-phase clinical trials.

This article reviews the longevity pharmacology landscape through the lens of actual evidence quality rather than hype. We examine what the Interventions Testing Program (ITP) has definitively shown, what metformin’s paradoxical human data means and whether the TAME trial will resolve it, how acarbose became an unexpected ITP standout, and what the first human senolytic trials have — and have not — demonstrated. Where relevant, Dr. Tom Biernacki connects these findings to the clinical management of diabetic peripheral neuropathy, metabolic disease, and the aging foot.

Table of Contents

• The Interventions Testing Program: The Gold Standard of Longevity Drug Testing
• Rapamycin: The Strongest ITP Signal and Its Clinical Translation Challenge
• Metformin: The TAME Trial and the Paradox That Started It All
• Acarbose: The Surprising ITP Standout
• Senolytics: Clearing the Cellular Debris of Aging
• Resveratrol, NAD+ Precursors, and Why Context Matters
• The Longevity Drug Stack: What Evidence-Based Clinical Practice Looks Like in 2026
• Pharmacology and Diabetic Peripheral Neuropathy
• Frequently Asked Questions
• The Bottom Line
• Sources

The Interventions Testing Program: Gold Standard Longevity Drug Testing

Before reviewing individual compounds, understanding the Interventions Testing Program (ITP) is essential context. Founded in 2004 with NIA funding, the ITP tests candidate longevity compounds simultaneously at three independent sites: University of Michigan, University of Texas Health Science Center San Antonio, and The Jackson Laboratory. All studies use genetically heterogeneous UM-HET3 mice (offspring of a four-way cross), which are more representative of natural genetic variation than inbred strains. All compounds are mixed into the diet at precisely controlled concentrations. All data must replicate across all three sites before claiming a positive result.

This design eliminates the major pitfalls that have made preclinical aging research notoriously unreliable: inbred strains with artificially compressed lifespans, single-site studies vulnerable to batch effects, and supplements added in ways that may affect caloric intake. The ITP is the reason we can discuss rapamycin and acarbose with genuine confidence — and why the null results for resveratrol, green tea extract, and many other popular “longevity supplements” carry real weight.

The ITP has now tested over 25 compounds. Positive results (significant lifespan extension in at least one sex at one or more sites, replicating across sites) have been found for: rapamycin, acarbose, 17-α-estradiol (males only), nordihydroguaiaretic acid (NDGA) (males only), canagliflozin (SGLT2 inhibitor — males only, 14% median lifespan extension in a 2020 result), and combinations including rapamycin + acarbose. Notably absent from the positive list despite enormous popular and industry interest: resveratrol, curcumin, fish oil, CoQ10, vitamin D3 at standard doses, and aspirin.

Rapamycin: The Strongest ITP Signal and Its Clinical Translation Challenge

Rapamycin (sirolimus) is the most robust longevity compound in the preclinical literature. The original Harrison et al. 2009 Nature paper showed 9–14% lifespan extension in genetically heterogeneous mice — even when treatment began at 20 months of age (equivalent to approximately 60 human years). Subsequent ITP cohorts using earlier start dates and higher doses achieved up to 23% median lifespan extension in females and 26% in males in some cohorts. No other single compound has replicated this effect size across multiple independent sites.

The mechanism is direct: rapamycin inhibits mTORC1, the growth-promoting kinase we discussed in the protein-leucine article. Chronic tonic mTORC1 activity drives cellular senescence, suppresses autophagy (the cellular housekeeping process that clears damaged proteins and organelles), promotes aging-associated tissue inflammation, and impairs stem cell quiescence. By dampening this tonic activity, rapamycin appears to shift cells toward a more maintenance-oriented state that accumulates damage more slowly.

The clinical challenge is rapamycin’s side effect profile in immunosuppressive doses: it was approved as an organ transplant antirejection drug at much higher continuous doses than are being explored for longevity applications. At transplant doses, rapamycin causes impaired wound healing, hyperlipidemia, thrombocytopenia, and immunosuppression. However, longevity researchers — most prominently Matt Kaeberlein at the University of Washington and Alan Green in clinical practice — are exploring intermittent low-dose rapamycin (typically 5–10mg once weekly) as a strategy that may preserve longevity benefits while minimizing immunosuppression. Kaeberlein’s Dog Aging Project has enrolled hundreds of companion dogs in a rapamycin trial to gather clinical data on this dosing strategy.

The mTORC1 vs. mTORC2 selectivity issue further complicates clinical translation. Many of rapamycin’s concerning side effects — glucose intolerance, impaired wound healing — appear to be mediated by off-target mTORC2 inhibition that occurs at higher doses or with chronic administration. Intermittent dosing may preserve mTORC1 inhibition (the desired longevity target) while allowing mTORC2 to recover during the off-days. This hypothesis is being actively tested but is not yet definitively established in human data.

As of 2026, rapamycin is not FDA-approved for longevity indications and its use for this purpose is off-label. The Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) trial and several other ongoing human trials aim to generate the safety and biomarker data needed to support broader clinical use. The current evidence base supports cautious interest but does not yet support widespread clinical prescription outside of research settings.

Metformin: The TAME Trial and the Paradox That Started It

Metformin’s longevity story begins with a striking epidemiological observation. A 2014 study by Bannister et al. in Diabetes, Obesity and Metabolism compared mortality in diabetic patients on metformin monotherapy to non-diabetic matched controls. The finding: metformin-treated diabetics outlived the non-diabetic controls — an effect size of approximately 15% lower all-cause mortality, despite diabetes itself being a significant mortality risk. This counterintuitive finding suggested that metformin was doing something beyond glucose control that might benefit even people without diabetes.

The mechanistic basis for metformin’s longevity effects extends far beyond its primary action as an AMPK activator that reduces hepatic glucose output. Metformin inhibits mitochondrial Complex I, reducing electron leak and reactive oxygen species production. It activates AMPK, which promotes mitophagy, inhibits mTORC1, and improves mitochondrial biogenesis via PGC-1α. It reduces systemic inflammation through NF-κB pathway inhibition. It enhances gut barrier function through Akkermansia muciniphila expansion (as discussed in our gut microbiome post). And it may have direct anti-senescence effects, with in vitro evidence showing metformin reduces the senescence-associated secretory phenotype (SASP) in cultured cells.

The ITP results for metformin are more mixed than the human epidemiology would suggest. In UM-HET3 mice, metformin starting at 9 months showed modest lifespan extension (4–5%) at one dose in males and did not replicate consistently across all sites or doses. The translational gap between the paradoxical human data and the modest murine data likely reflects species differences in AMPK pathway sensitivity and the fact that metformin’s gut-microbiome effects may be particularly relevant in human metabolic disease.

The TAME (Targeting Aging with Metformin) trial, launched under PI Nir Barzilai at Albert Einstein College of Medicine, is the first FDA-approved clinical trial with “aging” as a primary endpoint. Rather than targeting a specific disease, TAME measures a composite of age-related outcomes including cardiovascular events, cancer, dementia, and physical function decline. The trial enrolled approximately 3,000 adults ages 65–79 with at least one (but not two) major age-related comorbidities, randomized to 1,500mg/day metformin or placebo. Results are expected in the late 2020s. If positive, TAME would represent a regulatory milestone: the first clinical trial to validate aging as a treatable medical condition, potentially opening a regulatory pathway for future longevity drugs.

Acarbose: The Surprising ITP Standout

Acarbose does not feature prominently in longevity conversations — it lacks the name recognition of rapamycin, the global prescribing base of metformin, or the popular science narrative of senolytics. Yet its ITP results are remarkably consistent and mechanistically interesting.

Acarbose is an alpha-glucosidase inhibitor: it competitively blocks the intestinal enzyme that breaks down complex carbohydrates into glucose, substantially flattening the postprandial glucose spike without affecting fasting glucose or requiring insulin action. In the ITP, acarbose at 1,000ppm in the diet produced a 17% increase in median lifespan in males and approximately 5% in females — a sex-differential effect that has been reproduced in subsequent cohorts. When combined with rapamycin, the two compounds show additive or potentially synergistic effects, with some cohorts showing up to 28% lifespan extension.

The mechanistic question is why an intestinal enzyme inhibitor extends lifespan. Several non-mutually exclusive mechanisms have been proposed. First, the blunting of postprandial glucose spikes reduces glycation of proteins and DNA, reducing the AGE (advanced glycation end product) burden that accumulates with aging and drives vascular and neural damage. Second, acarbose substantially increases colonic fermentation of undigested carbohydrates, producing short-chain fatty acids (butyrate, propionate) that have the gut-longevity effects described in the microbiome article — including Akkermansia expansion and HDAC inhibition. Third, the caloric inefficiency introduced by carbohydrate malabsorption may produce a mild caloric restriction mimetic effect. Fourth, postprandial insulin spike suppression reduces chronic hyperinsulinemia, which drives mTORC1 tonic activation.

For patients with type 2 diabetes or impaired glucose tolerance, acarbose is FDA-approved (brand name Precose) and has a favorable safety profile — its primary side effects are GI (bloating, flatulence from increased colonic fermentation) and it does not cause hypoglycemia when used as monotherapy. The ITP finding raises the question of whether its longevity effects in non-diabetic individuals justify broader consideration, though no clinical trials in non-diabetic older adults for longevity endpoints currently exist.

SGLT2 Inhibitors: The ITP’s Newest Positive Signal

Canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes and heart failure, produced one of the ITP’s most recent positive results: 14% increase in median lifespan in males, with no significant effect in females, in a 2020 study (Miller et al., JCI Insight). SGLT2 inhibitors work by preventing glucose reabsorption in the kidney proximal tubule, causing glucose excretion in urine and reducing blood glucose independently of insulin.

The mechanistic basis for SGLT2 inhibitor longevity effects is likely multifactorial. Reduced glucose excretion means lower cellular glucose burden and reduced glycation. SGLT2 inhibitors activate AMPK and inhibit mTORC1 through pathways similar to metformin. They also reduce the activity of NLRP3 inflammasome — a key mediator of inflammaging — and improve mitochondrial function in cardiac and renal tissue. The clinical data on SGLT2 inhibitors in heart failure and chronic kidney disease show remarkable benefits that appear to extend beyond glucose control, consistent with pleiotropic longevity mechanisms.

The sex-differential (males only in ITP) is puzzling but consistent across the acarbose, canagliflozin, and NDGA results. The leading hypothesis involves sex differences in insulin sensitivity and baseline metabolic rate — male UM-HET3 mice may have greater baseline hyperglycemia and postprandial spike magnitude, making glucose-lowering interventions more impactful. Whether the sex differential translates to humans is unknown.

Senolytics: Clearing the Cellular Debris of Aging

Cellular senescence — the state in which cells permanently exit the cell cycle but resist apoptosis and secrete a cocktail of inflammatory mediators, matrix metalloproteinases, and growth factors known as the senescence-associated secretory phenotype (SASP) — is one of the hallmarks of aging with the strongest causal evidence for driving aging pathology.

The causal case was definitively made by a 2011 Nature paper from the Baker and van Deursen laboratories at Mayo Clinic. Using a genetic system that allowed selective clearance of p16-positive senescent cells in a mouse model of accelerated aging (INK-ATTAC mice), they demonstrated that clearing senescent cells delayed the onset of cataracts, sarcopenia, fat loss, and multiple organ dysfunction — and extended median lifespan. A 2016 follow-up in naturally aged wild-type mice showed that clearing senescent cells in middle age (starting at 12 months) extended lifespan and improved physical function even when treatment began after age-related decline was already apparent.

The pharmaceutical translation of this genetic finding led to the identification of senolytic drugs — small molecules that selectively induce apoptosis in senescent cells by targeting the anti-apoptotic pathways that allow them to resist cell death. The most studied senolytic combination is dasatinib + quercetin (D+Q). Dasatinib (a BCR-ABL tyrosine kinase inhibitor approved for leukemia) clears senescent adipocyte progenitors and some epithelial cells. Quercetin (a dietary flavonoid) adds complementary senolytic activity in endothelial cells and macrophages. Together, they produced 36% longer median remaining lifespan in mice treated starting at 24 months in a 2018 Nature Medicine paper (Xu et al.).

The first human senolytic trial was published in EBioMedicine (Kirkland et al., 2019): a pilot study in 14 patients with idiopathic pulmonary fibrosis (IPF), a lethal fibrotic lung disease with strong senescent cell involvement. Patients receiving 3 days of D+Q every 3 weeks for 9 total doses showed improvements in physical function (6-minute walk distance, chair stand speed, gait speed) alongside reductions in senescence biomarkers in adipose tissue biopsies. This was a small open-label study without a control arm — it cannot establish causality — but the direction and magnitude of effects were consistent with the mouse data and provided the first human proof-of-concept.

Subsequent human senolytic trials have examined D+Q in diabetic kidney disease, Alzheimer’s disease (Mayo Clinic), and frailty (multiple sites). As of 2026, results are mixed but promising in frailty endpoints. The clinical challenge is that dasatinib carries meaningful side effects at leukemia doses — the senolytic protocols use much lower intermittent doses (typically 100mg dasatinib + 1,000mg quercetin for 2–3 consecutive days per month) that appear to have more favorable tolerability. Fisetin, a flavonoid with senolytic activity, has completed early human trials and has a superior safety profile to dasatinib, though with less established efficacy.

The Evidence Graveyard: What the ITP Has Ruled Out

Understanding what has not worked in the ITP is as important as understanding what has. The program has tested and found null results for many of the most popular longevity supplements in commercial circulation. Resveratrol — the compound that launched a thousand longevity supplement companies after David Sinclair’s 2003 Nature paper on SIRT1 activation — failed to extend lifespan in the ITP despite extensive preclinical hype. The apparent effects in earlier studies appear to have been due to caloric restriction in obese mice rather than direct resveratrol action. Curcumin failed at multiple doses. Green tea extract was null. Aspirin showed a null result that surprised many researchers given its anti-inflammatory mechanism. Vitamin D3 at standard supplementation doses was null.

This does not mean these compounds have no health value — resveratrol has genuine cardiovascular and anti-inflammatory data outside of longevity endpoints, and vitamin D3 deficiency correction clearly matters for bone health, immunity, and mood. It means that the specific claim of lifespan extension via these compounds is not supported by the most rigorous preclinical testing system available. Consumers and clinicians should weigh this null ITP data appropriately when evaluating longevity supplement marketing.

Longevity Pharmacology and Diabetic Peripheral Neuropathy

Several longevity pharmacology candidates have specific relevance to the management of diabetic peripheral neuropathy (DPN) beyond their general aging effects.

Metformin and DPN: Beyond its glucose-lowering effects, metformin’s AMPK activation promotes mitochondrial biogenesis in peripheral nerve Schwann cells — the myelinating cells whose dysfunction is central to DPN progression. Its reduction of systemic inflammation decreases the TNF-α and IL-6 levels that drive neuroinflammation. Its Akkermansia-expansion gut effects reduce LPS endotoxemia, which activates TLR4-mediated Schwann cell inflammatory signaling. Multiple observational studies show lower DPN prevalence and slower progression in metformin-treated type 2 diabetes patients compared to those managed with other glucose-lowering agents — independent of HbA1c differences.

Canagliflozin/SGLT2 inhibitors and DPN: SGLT2 inhibitors’ ability to reduce NLRP3 inflammasome activation and improve mitochondrial function in neural tissue provides a direct neuroprotective mechanism. Cardiovascular outcome trials for SGLT2 inhibitors (CREDENCE, DAPA-CKD, EMPA-REG) have shown dramatic reductions in renal and cardiovascular events in type 2 diabetes — preserving vascular supply to peripheral nerves and reducing the ischemic component of DPN progression.

Senolytics and peripheral nerve regeneration: Senescent Schwann cells accumulate in diabetic peripheral nerves and secrete SASP factors that suppress axon regeneration and remyelination. Animal models of DPN show that senolytic clearance of these cells using D+Q or navitoclax improves nerve conduction velocity and nerve fiber density in a 2021 study (Zhang et al., PNAS). The first human DPN senolytic trial has not yet been completed as of 2026, but the mechanistic rationale is strong and clinical trials are being planned at several academic centers.

Acarbose and foot wound healing: Acarbose’s ability to reduce postprandial glucose spikes has specific wound healing relevance. Hyperglycemic episodes — even brief ones following meals — impair neutrophil function, reduce VEGF-mediated angiogenesis, and increase reactive oxygen species production in wound beds. Smoothing the postprandial glucose curve with acarbose may improve wound healing outcomes in ways that HbA1c alone does not capture, since HbA1c reflects average glucose rather than spike magnitude.

The Evidence-Based Longevity Drug Stack in 2026

What does an evidence-informed longevity pharmacology approach actually look like in clinical practice? This is not a recommendation for any individual — all pharmacological interventions require physician oversight — but a review of the current evidence-grade hierarchy for commonly considered compounds.

Tier 1: FDA-Approved with Longevity Epidemiology (Use If Clinically Indicated)

Metformin (for type 2 diabetes, pre-diabetes, or as off-label longevity consideration): Strongest human longevity data of any pharmaceutical. ITP data modest but multiple mechanisms support pleiotropic aging benefits. Bannister paradox remains unexplained but consistently replicated. Excellent safety profile, inexpensive, widely available. Potential concern: B12 depletion with long-term use (monitor and supplement).

SGLT2 inhibitors (for T2DM, heart failure, CKD): ITP lifespan data (canagliflozin, males +14%), combined with robust cardiovascular and renal outcome trial data (EMPA-REG, CREDENCE, DAPA-HF), makes SGLT2 inhibitors one of the most compelling evidence-based longevity drug classes available for patients with metabolic disease. Anti-inflammaging mechanisms (NLRP3 inhibition) may extend benefits beyond glucose control.

Acarbose (for T2DM or impaired glucose tolerance): ITP’s most consistent male longevity signal (17%). Postprandial glucose spike suppression, butyrate production augmentation, Akkermansia expansion. Primary barrier is GI tolerability — requires slow dose titration. Underused relative to evidence base.

Tier 2: Strong Preclinical Data, Early Human Evidence, Active Clinical Trials

Rapamycin (intermittent low-dose): Strongest ITP signal of any compound (10–23% lifespan extension, both sexes, replicates across sites, works even when started in old mice). Human trials ongoing. Current off-label use in longevity-focused clinical practices growing. Key uncertainty: optimal human dose and schedule for preserving mTORC1 benefits while minimizing mTORC2 and immunosuppressive effects.

Dasatinib + Quercetin (senolytics): Robust preclinical lifespan and healthspan data. Phase 1/2 human data in IPF, frailty, and DKD shows promising direction. Current protocol: D (100mg) + Q (1000mg) for 2 consecutive days every 2–4 weeks. Ongoing human trials will clarify efficacy in specific aging phenotypes over the next 3–5 years.

Tier 3: Mechanistically Sound, ITP Negative, Human Data Mixed

Resveratrol: ITP negative. Human cardiovascular meta-analyses mixed. Cannot recommend as longevity intervention. May have specific utility for specific indications (SIRT1 pathway in specific metabolic contexts) but whole-food polyphenol sources appear superior.

NMN/NR (NAD+ precursors): ITP not yet formally tested at optimal doses. Human RCT data shows NAD+ elevation confirmed (Yoshino 2021), with modest metabolic benefits. Not yet established as longevity-extending. Covered in detail in our NAD+ and Sirtuins article.

Frequently Asked Questions: Longevity Pharmacology

Is rapamycin safe to take for longevity?

At transplant-level continuous doses, rapamycin has significant side effects including immunosuppression, hyperlipidemia, and impaired wound healing. The question for longevity applications is whether intermittent low doses (5–10mg once weekly) can preserve the mTORC1 longevity benefits while avoiding immunosuppressive effects. Early human data from the Kaeberlein group and others suggests intermittent dosing is better tolerated than continuous dosing. However, as of 2026, there are no completed large human RCTs validating safety and efficacy for longevity indications — rapamycin for longevity remains an evidence-informed but off-label and experimental practice. Anyone considering it should do so under physician supervision with appropriate monitoring.

Should non-diabetics take metformin for longevity?

The TAME trial will provide the most definitive data on this question. Currently, metformin is FDA-approved only for diabetes/prediabetes. The Bannister paradox data is compelling but cannot establish causality in non-diabetic populations. Metformin’s primary concern in non-diabetics is potential interference with exercise adaptations — a 2020 NEJM evidence review (Konopka et al.) found that metformin blunted mitochondrial adaptations to exercise training in older adults, suggesting it may counteract one of the most evidence-based longevity interventions. This interaction is now considered a significant concern for active individuals considering non-diabetic metformin use. The practical guidance until TAME reports: if you have T2DM or prediabetes, metformin’s clinical benefit is established. For healthy non-diabetics, the exercise interference risk may outweigh the uncertain longevity benefit.

What is the TAME trial and when will results be available?

TAME (Targeting Aging with Metformin) is a double-blind, placebo-controlled RCT enrolling approximately 3,000 adults ages 65–79 at 14 academic sites across the United States. It is the first clinical trial to use “aging” itself as a composite primary endpoint — measuring the combination of time to first incident cardiovascular event, cancer, dementia, or physical disability. The trial received FDA Investigational New Drug approval, setting a regulatory precedent that aging can be treated as a medical indication. Enrollment began in 2021 and results are expected approximately 2028–2030. If positive, TAME could open regulatory pathways for future longevity drugs using the same composite aging endpoint.

Do senolytics actually work in humans?

The human senolytic data is preliminary but directionally promising. The 2019 Kirkland IPF pilot (14 patients, D+Q) showed functional improvements and senescence biomarker reduction. Subsequent trials in frailty, Alzheimer’s, and DKD are ongoing. The fundamental challenge is measuring senescent cell clearance in vivo — we do not yet have validated blood biomarkers for senescent cell burden the way we have troponin for myocardial injury. Until better biomarkers are validated, clinical trial design is challenging and results will remain harder to interpret. The 3-5 year outlook for senolytic human data is considered promising by most geroscientists, with the frailty trials likely to generate the first definitive positive or negative RCT results in humans.

How does the ITP decide which compounds to test?

The ITP accepts nominations from the scientific community, with a scientific advisory board evaluating submissions based on: strength of existing preclinical evidence, plausibility of the mechanism, safety profile suggesting human translation potential, and novelty (avoiding redundant testing of compounds with similar mechanisms). Researchers, physicians, and the public can submit nominations via the NIA’s ITP website. The process takes several years from nomination to results due to the lifespan study timeline. The ITP prioritizes compounds with realistic human translation pathways — explaining its focus on FDA-approved drugs (metformin, acarbose, SGLT2 inhibitors) alongside novel candidates.

The Bottom Line: Evidence Hierarchy in Longevity Pharmacology

The longevity pharmacology field is moving from speculation to rigor. The ITP provides the most credible preclinical evidence we have — and its results are both encouraging (rapamycin, acarbose, canagliflozin show real lifespan extension) and sobering (resveratrol, curcumin, aspirin, and dozens of popular supplements do not). Human clinical trials are active and accelerating, with TAME poised to become a regulatory milestone.

The practical clinical picture for 2026 is this: if you have type 2 diabetes or prediabetes, metformin, SGLT2 inhibitors, and acarbose each have evidence supporting benefits that extend well beyond glucose control into genuine aging biology territory. These are not experimental — they are FDA-approved, widely prescribed, relatively safe, and supported by some of the strongest longevity pharmacology data available. The TAME trial will clarify whether metformin’s benefits extend to people without diabetes. Rapamycin and senolytics remain experimental and require physician supervision and ongoing monitoring.

For patients with diabetic peripheral neuropathy specifically, the convergence of metformin, SGLT2 inhibitors, and (potentially) senolytics on peripheral nerve pathways — through AMPK activation, NLRP3 suppression, and senescent Schwann cell clearance respectively — represents a pharmacological complement to lifestyle interventions that deserve serious consideration as part of an integrated DPN management plan.

Sources and Further Reading

• Harrison DE, et al. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 460(7253), 392–395.
• Miller RA, et al. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. Journals of Gerontology Series A, 66(2), 191–201.
• Bannister CA, et al. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes, Obesity and Metabolism, 16(11), 1165–1173.
• Strong R, et al. (2016). Longer lifespan in male mice treated with a weakly estrogenic compound, the isoflavone daidzein, is not caused by caloric restriction. Journals of Gerontology Series A [ITP acarbose report].
• Miller RA, et al. (2020). Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI Insight, 5(21):e140019.
• Baker DJ, et al. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232–236.
• Xu M, et al. (2018). Senolytics improve physical function and increase lifespan in old age. Nature Medicine, 24(8), 1246–1256.
• Justice JN, et al. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 40, 554–563.
• Konopka AR, et al. (2020). Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell, 18(2), e12880.
• Kaeberlein M, et al. (2013). The Biology of Aging: Citizen Scientists and Their Pets as a Bridge Between Research on Model Organisms and Human Aging. Human Genetics.
• Barzilai N, et al. (2016). Metformin as a Tool to Target Aging. Cell Metabolism, 23(6), 1060–1065. [TAME trial rationale]

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