#207 - AMA #35: "Anti-Aging" Drugs — NAD+, metformin, & rapamycin
This AMA episode features Dr. Matt Kaeberlein, a professor at the University of Washington, who joins Peter Attia to discuss the field of aging. They focus on geroprotective molecules like NAD, rapamycin, and metformin, along with aging biomarkers and epigenetic clocks, to help listeners critically evaluate new data.
Deep Dive Analysis
7 Topic Outline
Introduction to AMA 35 and guest Matt Kaeberlein
Rationale for comparing NAD, rapamycin, and metformin
Current state and usefulness of aging biomarkers
Challenges and limitations in identifying aging biomarkers
Defining and explaining epigenetic clocks
Limitations and concerns regarding epigenetic clocks
Commercialization and ethical issues of aging clocks
2 Key Concepts
Biomarkers of Biological Aging
These are measurable indicators that predict future health outcomes, mortality, functional outcomes, or disease risk at an individual or population level. The ideal biomarker should reflect biological age and potentially the rate of aging or reversal of aging.
Epigenetic Clocks
These are algorithms that predict an individual's chronological age based on chemical modifications (like methylation) to DNA or to the histones that pack the DNA, which in turn control gene expression. They aim to identify individuals whose biological age deviates from their chronological age, potentially predicting future health risks.
8 Questions Answered
These three molecules are frequently discussed as leading candidates for geroprotectors, and comparing their current data helps understand the evidence for each and the challenges in moving them from the laboratory into clinical application.
While humans can visually estimate biological age to some extent, the field of molecular biomarkers for aging is still a work in progress, with no perfect measures that precisely predict an individual's biological aging trajectory or rate of aging.
An ideal biomarker should be measurable and predictive at either the individual or population level for future health outcomes such as mortality, functional outcomes, and disease risk.
Epigenetic clocks are algorithms that predict chronological age by measuring age-related changes in chemical modifications (like methylation) to DNA or histones. They aim to identify individuals whose biological age differs from their chronological age, potentially predicting future health risks.
There are about two dozen different epigenetic clocks, making it unclear which are best. A significant limitation is the lack of definitive experiments, even in mice, showing that these clocks can predict future health outcomes in the same individual, especially given the dramatic changes in human environments over time.
Despite the relative ease of conducting lifespan studies in mice, a definitive experiment demonstrating that epigenetic clocks can predict individual or population-level survival and pathology well in advance of end-of-life has not been performed, which represents a significant gap in the scientific literature.
Epigenetic clocks specifically focus on methylation patterns on DNA, while broader aging clocks incorporate a wider range of biomarkers, including traditional clinical markers like vitamin D levels and fasting glucose, potentially offering a more comprehensive picture of an individual's biological age.
Selling the idea that biological age can be measured with precision and used to guide interventions is often dishonest, particularly when companies also sell products claiming to reverse biological age, which is described as 'snake oil' and warrants regulatory intervention.
4 Actionable Insights
1. Track Functional Health Markers
To gauge progress in health and longevity, focus on improving functional markers such as VO2 max, muscle mass, strength, cardiovascular efficiency, glucose disposal, insulin signaling, ApoB, lipid markers, and inflammatory markers.
2. Beware Commercial Aging Clocks
Exercise caution regarding commercial ‘aging clocks’ and products that claim to reverse biological age, as the scientific community views these claims as dishonest and lacking precision.
3. Consult Healthcare Professionals
Remember that this podcast provides general information only and is not a substitute for professional medical advice; always consult your healthcare professional for any medical conditions.
4. Watch Full Podcast Video
Subscribers can find the full video of the podcast on the show notes page; non-subscribers can watch a sneak peek on YouTube.
5 Key Quotes
If your objective is to lower ApoB, because ApoB plays a causative role in atherosclerotic cardiovascular disease, you have the perfect biomarker. It's ApoB.
Peter Attia
What I think you really want is something you can measure that is predictive at either the individual or the population level of future health outcomes. Mortality, certainly, but also functional outcomes, disease risk, things like that.
Matt Kaeberlein
I just have a hard time believing that there's going to be an epigenetic signature that I think will be more valuable than some of the most tried and true phenotypic tests. VO2 max, zone two threshold, grip strength, muscle mass, fat free mass index, all of these sorts of things that are so highly, and I believe causally linked to longevity.
Peter Attia
It's just frankly dishonest. Now, some people will argue that it's a necessary evil in the sense that one, it broadens the appeal of the field to the general public. And two, it's causing people to make healthy lifestyle choices. Maybe when you measure your biological age and it tells you you're 10 years older than your chronological age, you start exercising or you eat better. Maybe that's true. I don't know that that's necessarily true, but it's still dishonest to claim to people that anyone is able to, with any precision, measure your biological age.
Matt Kaeberlein
It becomes a bigger problem when the same companies are then also selling a product that they claim will reverse your biological age. That's just snake oil. I don't know any other way to say it. It's just snake oil. Honestly, the FDA should step in and do something about it, in my opinion.
Matt Kaeberlein