Prompt Cast
Understanding Aging Biology and Interventions: Rapamycin, NAD, and More
TLDR Exploring the biology of aging, interventions like rapamycin and NAD precursors show promise in reversing age-related declines, enhancing health, and potentially extending lifespan in mice and dogs, with implications for human aging and disease prevention. Researchers are investigating biomarkers, multiomic analysis, and machine learning to predict intervention effects, paving the way for streamlined drug discovery processes and clinical trials in the future.
Timestamped Summary
00:00
The episode delves into the biology of aging, rapamycin, and interventions targeting aging processes, discussing hallmarks of aging, wrap-up mice, rapalogs, Torin-2, Sertuans, NAD, NR, and NMN.
08:43
Functional declines that precede overt disease or clinical diagnosis are significant indicators of aging and quality of life, often occurring before age-related diseases manifest.
16:50
Biological age is the single greatest risk factor for every major cause of death and disability, regardless of whether aging directly causes diseases or creates a permissive state for their manifestation.
25:03
Targeting the biology of aging to enhance health and longevity is the focus of 21st-century medicine, with interventions showing potential to reverse age-related declines in mice.
33:36
Rapamycin has shown potential to reverse age-related declines in mice and extend lifespan, but the optimal treatment period and dosing schedule for humans remains uncertain due to the lack of long-term controlled clinical trials.
41:41
Rapamycin has shown the potential to fully restore immune function in older mice, making them 100% effective at responding to vaccines, which has implications for understanding immune responses in older adults and COVID vaccination.
49:59
mTOR inhibitors like rapamycin may help reduce organ rejection in transplant patients and target inappropriate immune activation in aging physiology.
58:05
RTB-101, an mTOR complex one inhibitor, showed promise in improving vaccine response and reducing the risk of upper respiratory tract infections in older adults without significant side effects, despite a failed phase three clinical trial.
01:06:39
Regulators may allow clinical trials with Rapamycin for aging interventions, but identifying the right endpoints for such trials remains a challenge.
01:14:48
A potential clinical trial involving rapamycin aims to assess its impact on age-related periodontal disease in humans, inspired by successful results in mice.
01:22:20
Rapamycin may have anti-inflammatory effects that improve range of motion in conditions like frozen shoulder, potentially resetting age-related inflammatory conditions with an eight-week treatment.
01:29:56
Biomarkers such as telomere length and epigenetic clocks are being used to assess biological age and predict disease risk, but concerns remain about their reliability and ability to provide mechanistic insights into the aging process.
01:37:44
Researchers are exploring the use of multiomic analysis and machine learning to predict the effects of interventions on aging in mice, potentially paving the way for more streamlined drug discovery processes and clinical trials in the future.
01:45:44
Dogs, due to their rapid aging process and shared environment with humans, serve as a valuable animal model for studying aging and testing interventions, such as the ongoing clinical trial testing rapamycin's effects on lifespan in dogs.
01:53:47
Rapamycin has shown to reverse age-related declines in heart function in mice and dogs, particularly in those with lower baseline function.
02:02:25
Rapamycin's effects on mTOR complex two and glucose tolerance are still not entirely clear, with some evidence suggesting a link to metabolic side effects, but the overall impact on glucose homeostasis may reflect a metabolic adaptation rather than a negative outcome.
02:10:49
Testing Torrin 2 in mice for aging effects and potential benefits in mitochondrial disease models shows promising results and suggests a need for further exploration.
02:18:49
Interventions effective in severe mitochondrial disease models may also be effective in normative aging, suggesting potential for catalytic inhibitors of mTOR like Torin 2 to be explored further for aging-related indications.
02:26:57
Boosting NAD levels through precursors like nicotinamide riboside and nicotinamide mononucleotide may potentially restore sirtuins activity and impact aging, although biological efficacy and reproducibility remain uncertain.
02:34:57
Testing the impact of NAD precursors on aging in pet dogs could provide valuable insights for potential human interventions.
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Health & Fitness
