Prompt Cast
Longevity, Aging Research, and Metformin: Insights from Nir Barzilai
TLDR Nir Barzilai discusses the role of metformin, insulin resistance, IGF, growth hormone, and centenarian studies in aging research, highlighting the potential impact of targeting aging to prevent age-related diseases and the genetic factors influencing longevity. The episode also explores the complexities of hormone replacement studies, the effects of metformin on metabolic parameters, and the need for more clinical studies to validate claims about NAD precursors.
Timestamped Summary
00:00
The episode features Nir Barzilai, a leading expert in longevity and aging research, discussing topics such as metformin, insulin resistance, IGF, growth hormone, and centenarian studies.
08:15
Hormonal changes with aging, particularly in women, were initially focused on, but broader considerations including thyroid hormones and other factors were also explored, leading to discussions on the Women's Health Initiative and the complexities of hormone replacement studies.
17:06
Metformin's role in glucose disposal and insulin sensitivity, particularly in the context of aging, was discussed alongside the impact of insulin resistance on longevity based on studies in nematodes.
26:03
Insulin resistance was found to be a protective mechanism affecting longevity in animal models, with the removal of visceral fat leading to increased lifespan in rats.
34:38
Insulin resistance is defined by the ability of insulin to clear glucose in the muscle, impacting glucose uptake and sensitivity.
43:32
The difference in hyperinsulinemia and its impact on insulin resistance is not widely considered in clinical practice, with insulin rarely being measured in type two diabetic patients, potentially leading to different health outcomes related to glucose disposal and vascular diseases.
52:27
A study comparing patients on sulfonylurea and metformin for diabetes showed that those on metformin had significantly lower mortality rates, indicating a potential important effect of metformin on aging.
01:01:21
A group of professors engaged in discussions with the FDA to emphasize the importance of targeting aging to prevent a range of age-related diseases, despite the FDA's initial lack of interest in diabetes outcomes.
01:09:51
The TAME study aims to target aging by enrolling 3000 subjects aged 65 to 80 in early 2019 to test the effects of metformin on aging-related diseases, with funding from various sources including philanthropy and pharmaceutical companies.
01:18:54
Metformin impacts aging by affecting AMP kinase, mTOR activity, and autophagy, leading to changes in mitochondrial function and cellular aging.
01:28:03
Centenarians have a genetic gift of a phase shift that allows them to live longer, healthier lives with a compression of morbidity, leading to significant potential societal benefits.
01:36:11
A U-shaped mortality curve was found between the 60th and 80th percentile of all-cause mortality, with individuals aging quickly showing falsely low IGF levels, highlighting the importance of sex differences and genetic mutations in IGF receptors for longevity.
01:45:33
Individuals with lower IGF levels due to a mutation in the growth hormone receptor showed dysfunction in the receptor, leading to lower IGF levels and further studies validated this mutation's impact on longevity.
01:54:50
Centenarians with certain genetic mutations, such as CTP VV, show protective phenotypes against age-related diseases, including cognitive decline, and have higher levels of LPLittle A, suggesting a potential link between longevity genes and lipid profiles.
02:04:27
The interaction between LP little A and CTP levels may impact aging and disease risk, with potential implications for manipulating IGF and growth hormone for longevity.
02:12:57
The impact of sex hormones on inflammation and aging, the potential protective effects of estrogen, progesterone, and testosterone, and the role of fasting in manipulating IGF levels for longevity are being explored.
02:21:39
Metformin showed significant effects on metabolic parameters in a small clinical study involving 75-year-old individuals, with better results observed in those who transitioned from placebo to metformin compared to their peers.
02:30:14
The discussion delves into the uncertainty surrounding the efficacy of orally administered nicotinamide riboside in reaching cells, highlighting the need for more clinical studies to validate claims made by various companies selling NAD precursors.
02:39:15
Recruiting for the study has been selective, with participants showing interest in the potential benefits of the study's focus on aging, but the study has not yet been conducted, emphasizing the need for caution and further research.
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Health & Fitness
