204 - Centenarians, metformin, and longevity | Nir Barzilai, M.D.

A groundbreaking clinical trial designed to test metformin's efficacy as a geroprotective agent in non-diabetic elderly individuals, with a primary outcome focused on a cluster of age-related diseases and mortality.

A large-scale biomedical database that has significantly advanced the ability to validate and generate hypotheses in longevity research, notably used to study IGF-1 levels across different age groups.

An NIH-funded clinical study that used metformin as one of its arms to prevent diabetes, showing significant benefits and providing early evidence for metformin's broader effects.

An early, more potent and toxic form of metformin that caused side effects due to its strong mitochondrial action.

A drug commonly used for type 2 diabetes, now being studied for its potential geroprotective effects, stemming from observations of lower mortality and disease rates in diabetics taking it.

A class of drugs mentioned as one of the three 'best drugs in the world' (along with Rapamycin and Metformin) with nutraceutical origins, despite being prescription medications.

A well-known gerotherapeutic agent, often compared with metformin, with strong evidence for longevity extension in animal models, particularly through the ITP studies.

An observation from World War II stating that babies born small for gestational age tend to develop age-related diseases more rapidly.

A gene involved in lipid metabolism, specific genotypes of which were found to be elevated in centenarians, potentially contributing to longevity.

A gene that came to light from Okinawa studies and is considered part of the insulin signaling pathway, found in 60% of centenarians and associated with longevity.

A hormone whose signaling pathway, along with growth hormone, is impaired in 60% of centenarians, suggesting its role in human longevity via a delicate balance that changes with age.

A protective peptide that increases significantly in people taking metformin, suggested as a potential biomarker for metformin compliance and aging.

A genetic variant associated with a major risk factor for Alzheimer's disease, but found in some centenarians without cognitive impairment, suggesting other protective genes or mechanisms.

A gene (or its variants) that showed a U-shaped longevity curve in centenarians, suggesting that while some variants may be detrimental at younger ages, other protective mechanisms or variants render it irrelevant later in life.

A nematode, one of the simplest organisms where changing a single gene (like the insulin receptor) can lead to significantly extended lifespan, serving as an initial inspiration for longevity research.

A gene, discussed alongside APOE4 and mitochondrial haplotypes, as part of a polygenic approach to assessing risk for Alzheimer's disease.

A theory of aging that suggests traits beneficial early in life (like high IGF-1 for growth) can become detrimental later in life, driving further age-related decline or disease.

Individuals with a deletion of the growth hormone receptor, who exhibit less age-related diseases like cancer and diabetes, but are also shorter and face other health challenges.

The plant from which metformin is an extract, illustrating its nutraceutical origin before chemical modification into a pharmaceutical drug.

Hasey Cohen, dean of gerontology at USC, is a collaborator who studied the growth hormone receptor deletion phenotype in centenarian lymphoblasts.

A highly rigorous study conducted in mice, independently across three labs, known for its all-cause mortality endpoint. Metformin alone did not show strong longevity benefits in ITP, raising questions about species differences or dosing.

An organization that received a significant donation to fund a large-scale study recruiting 10,000 centenarians and their offspring for genetic analysis, aiming to accelerate longevity research.

The NIH institute that funded a portion of the DPP study to include elderly subjects, and is also providing grants for biomarker research related to the TAME study.

A researcher known for his work on the Interventions Testing Program (ITP), whose findings on metformin's efficacy in mice are discussed in contrast to human data.

Co-author of a 2013 paper on metformin in mice, criticized for presenting a statistically insignificant longevity benefit as definitive evidence.

Runs the longevity studies and measured IGF-1 levels in centenarians, contributing to findings on sex-specific effects of IGF-1 on longevity.

Host of The Drive podcast, a physician and interviewer, facilitating the discussion on longevity, centenarians, and various interventions.

A developer of epigenetic clocks, mentioned in the context of the challenges and limitations of these biological age markers.

Guest on the podcast, a physician and expert in longevity research, discussing his studies on centenarians and interventions like metformin.

Researcher mentioned as a key figure, along with Dr. Barzilai, in studying centenarians and their unique characteristics.

His discussion with Peter Attia on CETP inhibitors and HDL biology was referenced, indicating a complex understanding of HDL function beyond simple cholesterol levels.

A researcher focused on Alzheimer's disease mentioned in the context of polygenic risk scores and the evolving understanding of APOE4's impact on dementia risk.

Popularized the NAD+ precursor research, mentioned in the context of NMN preparations and costs.

A collaborator of Dr. Barzilai who conducts functional genetic studies, analyzing the resilience of genes to injury to understand longevity mechanisms.

A researcher at Yale with whom Dr. Barzilai worked as a fellow, tasked with describing the mechanisms of action of metformin in humans.

An NAD+ biologist from European who hypothesized that NAD+ precursors ingested orally primarily affect the microbiome rather than directly increasing systemic NAD+ levels.

A computational biologist mentioned as a key team member whose work contributes significantly to Dr. Barzilai's studies.

A researcher whose papers on metformin and exercise were reviewed, showing that while metformin may reduce muscle hypertrophy, it can lead to healthier, biologically younger muscle.

A scientist working on epigenetic clocks, who is described as having a mechanistic approach to epigenetics, contrasting with purely correlational clocks.

A drug referred to as undergoing studies similar to metformin for its effects on muscle transcriptome and aging.

A compound mentioned in the context of interventions studied for their impact on muscle transcriptome, showing effects similar to metformin and acarbose.

Nutraceuticals widely discussed for their potential geroprotective effects, though the biological mechanisms and human efficacy remain unclear and unproven, with inconsistent personal experiences reported.

A NAD+ precursor that Dr. Barzilai personally experimented with, noting a temporary improvement in REM sleep but ultimately remaining unconvinced of its overall efficacy due to unclear biology and inconsistent results.

A class of cholesterol-lowering drugs mentioned to highlight the high cost of certain NMN supplements, comparing them to expensive pharmaceuticals.

A database or accumulation of genes and variants known to cause diseases, used by researchers to analyze the genomes of centenarians for disease-causing variants.

A region in Japan where FOXO3A was initially identified as a gene associated with longevity, prompting broader research into its effects.

A company that paid for the genotyping in Dr. Barzilai's centenarian studies, leading to reduced direct costs for the research.

A drug company that explored CETP inhibitors; asked by Dr. Barzilai to conduct cognitive function studies related to these drugs, which were done on a younger population.