#175 - Matt Kaeberlein, Ph.D.: The biology of aging, rapamycin, and other interventions that target the aging process | The Peter Attia Drive

This podcast explores the complexities of aging, contrasting molecular definitions with functional perspectives like frailty. Matt Kaeberlein, a leading aging researcher, joins Peter Attia to discuss the hallmarks of aging, the role of disease, and the challenges of translating interventions from animal models to human clinical trials. They examine the nuances of rapamycin, including dosing strategies and potential immune effects, and debate whether its benefits stem from direct immune suppression or broader anti-inflammatory action. The discussion also covers the potential of TORIN2, a catalytic mTOR inhibitor, and the controversies surrounding NAD precursors and sirtuin activation. The conversation emphasizes the need for better biomarkers and regulatory frameworks to advance aging research and interventions.

Outlines

Part 1: Defining Aging and Disease

Part 2: Rapamycin and Clinical Challenges

Part 3: Trials, Endpoints, and Biomarkers

Part 4: The Dog Aging Project

Part 5: mTOR Mechanisms and Future Research

Part 6: Sirtuins, NAD, and Conclusions

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#175 - Matt Kaeberlein, Ph.D.: The biology of aging, rapamycin, and other interventions that target the aging process

The Peter Attia Drive

Part 1: Defining Aging and Disease

Defining Aging: Molecular Damage, Functional Decline, and Biological Perspectives

Hallmarks of Aging, Disease, and Functional Decline: Intertwined Perspectives

Age as the Primary Risk Factor: Disease-Specific vs. Foundational Approaches

Part 2: Rapamycin and Clinical Challenges

Centenarians, Disease Delay, and the Challenges of Studying Aging in Humans

Rapamycin Dosing Strategies: Balancing Benefits, Risks, and Clinical Trial Data

Rapamycin, Immune Function, and the Failure of the RestoreBio Phase 3 Trial

RTB-101, Regulatory Hurdles, and the Definition of "Healthy" Aging

Part 3: Trials, Endpoints, and Biomarkers

TAME, Clinical Trial Endpoints, and Periodontal Disease as a Target

Secondary Endpoints, Hearing Loss, and Personal Experiences with Rapamycin

Biomarkers of Aging: Epigenetic Clocks, Multi-Omics, and the NIA's Efforts

Part 4: The Dog Aging Project

Dog Aging Project: Genetics, Environment, and Lifespan Diversity

TRIAD Study Design: Endpoints, Dosing, and the Importance of Minimizing Side Effects

Part 5: mTOR Mechanisms and Future Research

mTOR Complex 1 vs. mTOR Complex 2: Function, Inhibition, and Metabolic Effects

TORIN2: A Catalytic Inhibitor of mTOR and a Potential Therapeutic Target

Mitochondrial Disease, Rapamycin, and the Potential of TORIN2

Part 6: Sirtuins, NAD, and Conclusions

Sirtuins, NAD Precursors, and the Importance of Reproducible Results

The Future of Aging Research: Clinical Trials, Dog Studies, and Gratitude

#175 - Matt Kaeberlein, Ph.D.: The biology of aging, rapamycin, and other interventions that target the aging process

The Peter Attia Drive

Part 1: Defining Aging and Disease

00:10Defining Aging: Molecular Damage, Functional Decline, and Biological Perspectives

Defining Aging: Molecular Damage, Functional Decline, and Biological Perspectives

07:22Hallmarks of Aging, Disease, and Functional Decline: Intertwined Perspectives

Hallmarks of Aging, Disease, and Functional Decline: Intertwined Perspectives

17:57Age as the Primary Risk Factor: Disease-Specific vs. Foundational Approaches

Age as the Primary Risk Factor: Disease-Specific vs. Foundational Approaches

Part 2: Rapamycin and Clinical Challenges

25:27Centenarians, Disease Delay, and the Challenges of Studying Aging in Humans

Centenarians, Disease Delay, and the Challenges of Studying Aging in Humans

34:28Rapamycin Dosing Strategies: Balancing Benefits, Risks, and Clinical Trial Data

Rapamycin Dosing Strategies: Balancing Benefits, Risks, and Clinical Trial Data

47:16Rapamycin, Immune Function, and the Failure of the RestoreBio Phase 3 Trial

Rapamycin, Immune Function, and the Failure of the RestoreBio Phase 3 Trial

55:29RTB-101, Regulatory Hurdles, and the Definition of "Healthy" Aging

RTB-101, Regulatory Hurdles, and the Definition of "Healthy" Aging

Part 3: Trials, Endpoints, and Biomarkers

1:07:09TAME, Clinical Trial Endpoints, and Periodontal Disease as a Target

TAME, Clinical Trial Endpoints, and Periodontal Disease as a Target

1:15:06Secondary Endpoints, Hearing Loss, and Personal Experiences with Rapamycin

Secondary Endpoints, Hearing Loss, and Personal Experiences with Rapamycin

1:27:28Biomarkers of Aging: Epigenetic Clocks, Multi-Omics, and the NIA's Efforts

Biomarkers of Aging: Epigenetic Clocks, Multi-Omics, and the NIA's Efforts

Part 4: The Dog Aging Project

1:39:07Dog Aging Project: Genetics, Environment, and Lifespan Diversity

Dog Aging Project: Genetics, Environment, and Lifespan Diversity

1:47:41TRIAD Study Design: Endpoints, Dosing, and the Importance of Minimizing Side Effects

TRIAD Study Design: Endpoints, Dosing, and the Importance of Minimizing Side Effects

Part 5: mTOR Mechanisms and Future Research

1:59:01mTOR Complex 1 vs. mTOR Complex 2: Function, Inhibition, and Metabolic Effects

mTOR Complex 1 vs. mTOR Complex 2: Function, Inhibition, and Metabolic Effects

2:07:07TORIN2: A Catalytic Inhibitor of mTOR and a Potential Therapeutic Target

TORIN2: A Catalytic Inhibitor of mTOR and a Potential Therapeutic Target

2:11:15Mitochondrial Disease, Rapamycin, and the Potential of TORIN2

Mitochondrial Disease, Rapamycin, and the Potential of TORIN2

Part 6: Sirtuins, NAD, and Conclusions

2:20:05Sirtuins, NAD Precursors, and the Importance of Reproducible Results

Sirtuins, NAD Precursors, and the Importance of Reproducible Results

2:35:01The Future of Aging Research: Clinical Trials, Dog Studies, and Gratitude

The Future of Aging Research: Clinical Trials, Dog Studies, and Gratitude