Why is it difficult to find good biomarkers for aging?

Unlike fields like lipidology with clear biomarkers like ApoB, aging research lacks a single, universally accepted biomarker. While some candidates exist, researchers debate their predictive accuracy for future health outcomes and mortality.

What are epigenetic clocks and how do they work?

Epigenetic clocks are algorithms that analyze chemical modifications to DNA (like methylation) to predict a biological age. They are based on the observation that these marks change predictably with chronological age and can correlate with future health risks.

What are the limitations of epigenetic clocks?

Limitations include the existence of many different clocks, the reliance on a subset of aging processes, and the lack of definitive lifespan studies in humans showing predictive power for interventions. The influence of environmental changes on epigenetic marks also complicates interpretation.

Are epigenetic clocks validated by lifespan studies in mice?

Matt Calcott points out that definitive lifespan studies for epigenetic clocks in mice are notably absent, which is a significant gap in the literature despite the relative ease of conducting such experiments.

Should I trust companies selling biological age tests?

The podcast hosts express strong concern about the commercialization of aging clocks. They advise caution, stating that claims of accurately measuring biological age and selling products to reverse it are often dishonest and akin to 'snake oil.'

How should I interpret studies on aging interventions like NAD+, Rapamycin, or Metformin?

When interpreting studies, consider the model used (mice, yeast, humans), the specific biomarkers measured, and the limitations. Focus on functional outcomes and be wary of commercial claims that may overstate the current scientific certainty.

Key Moments

"Anti-Aging" Drugs — NAD, metformin, & rapamycin | The Peter Attia Drive Podcast (Ep 207, AMA 35)

Peter Attia MD

Science & Technology3 min read30 min video

May 16, 2022|77,495 views|1,408|135

anti-aging drugs anti-aging NAD metformin rapamycin longevity drugs longevity nad iv therapy epigenetic clocks

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Key Moments

TL;DR

Discusses NAD+, metformin, rapamycin, and aging biomarkers, highlighting data limitations and commercialization concerns.

Key Insights

Assessing biological age is challenging due to a lack of definitive predictive biomarkers.

Epigenetic clocks show promise but require validation through longitudinal lifespan studies in humans and animals.

Functional biomarkers and phenotypic improvements offer more reliable, albeit cruder, indicators of aging intervention efficacy.

Commercialization of aging clocks and related products raises ethical concerns about misleading claims and 'snake oil'.

The 'Hallmarks of Aging' suggest a multi-faceted approach is needed, not solely focused on epigenetics.

Interpreting studies on geroprotective molecules requires understanding their limitations and the context of aging research.

THE COMPLEXITY OF AGING BIOMARKERS

The discussion begins by highlighting the difficulty in finding reliable biomarkers for aging, contrasting it with fields like lipidology where clear targets like ApoB exist. While humans can often intuitively assess biological age, precise, universally accepted molecular biomarkers remain elusive. The field is a work in progress, with ongoing debate about the accuracy and predictive power of current candidates, especially as 'aging clocks' enter the commercial market.

THE PROMISE AND PITFALLS OF EPIGENETIC CLOCKS

Epigenetic clocks, which measure chemical modifications to DNA and histones that influence gene expression, are a significant focus. These clocks can predict chronological age with high accuracy, leading to the hypothesis that deviations from this prediction indicate biological age. While longitudinal studies show correlations between younger epigenetic age and better future health outcomes, the lack of definitive, completed lifespan studies in mice and humans raises concerns about their ultimate predictive power and relevance in today's changing environment.

FUNCTIONAL VS. MOLECULAR MARKERS

A key distinction is made between biomarkers that reflect biological age and those that indicate the rate of aging or potential reversal. While blood-based molecular markers are desired for practical reasons, functional biomarkers assessing organ and tissue performance are considered more reliable indicators of health outcomes. Improvements in VO2 max, muscle mass, strength, and cardiovascular efficiency are seen as tangible evidence of positive intervention effects, serving as a more pragmatic approach in clinical practice.

BROADER AGING CLOCKS AND HOLISTIC VIEWS

The conversation explores the idea that 'aging clocks' incorporating a broader range of traditional biomarkers (e.g., Vitamin D levels, fasting glucose) alongside epigenetic data may offer a more holistic picture. Since aging is characterized by multiple 'Hallmarks,' a clock that considers only one aspect, like epigenetics, risks being incomplete. This broader approach is considered more likely to capture the multifaceted nature of biological aging at an individual level, though precision remains a challenge.

CONCERNS ABOUT COMMERCIALIZATION AND MISLEADING CLAIMS

A significant concern raised is the premature commercialization of aging clocks and related interventions. Presenting these clocks as accurately measuring biological age, especially when marketed to the general public, is deemed dishonest. The practice of pairing aging clocks with supplements or interventions and then claiming reversal of biological age is criticized as 'snake oil,' with a call for regulatory bodies like the FDA to intervene due to the potential for misleading the public.

INTERPRETING STUDIES ON GEROPROTECTIVE MOLECULES

Given the complexities of aging biomarkers, interpreting studies on geroprotective molecules like NAD+, metformin, and rapamycin requires careful consideration. Listeners are advised to understand the limitations of current research, the models used (e.g., mice, yeast, humans), and the specific outcomes measured. The discussion aims to provide a clearer understanding of the evidence base for these molecules, acknowledging both their potential and the significant gaps in knowledge that still exist.

Mentioned in This Episode

●Supplements

●Software & Apps

●Organizations

●Concepts

●People Referenced

Common Questions

The main geroprotective molecules discussed are NAD+ and its precursors (NR, NMN), Rapamycin, and Metformin. These are considered leading candidates for slowing or reversing aspects of aging.