Irina Conboy: We've Been Measuring Aging All Wrong
Irina Conboy and Generation Lab co-founder Alina Su argue that popular epigenetic clocks are simplified data-fitting exercises, not real measurements. They present System Age, which tracks rising instability in homeostatically vital genes, and discuss plasma dilution, organ-chip experiments and a dual-action therapeutic.
Overview
Matt Kaeberlein hosts Irina Conboy, a pioneer of heterochronic parabiosis, and Alina Su, co-founder of Generation Lab. They trace how the company grew from Conboy's Berkeley lab to a full-time venture, and revisit the classic work showing that shared circulation makes old tissues younger and young tissues older. Conboy explains why young blood is not the secret sauce, why simply diluting old plasma drives rejuvenation, and how human organ chips age fresh stem-cell tissue within four days of exposure to old serum.
Kaeberlein and Conboy debate rapamycin, absolute versus percent lifespan, and what has actually been proven in humans. Conboy delivers a pointed critique of epigenetic clocks, arguing they replace real biology with biologically arbitrary weights. She then describes System Age, which measures rising variability in vital genes rather than fitting a trajectory, and maps that instability to 21 body systems. The conversation closes on male-female aging differences, environmental exposures, at-home testing, and why the goal is not a single number but knowing which system is aging and what to do about it.
Key quotes
5If we can solve aging itself, why don't we target that root cause, because it's causing 80% of all disease?
Just four days of circulating blood serum from old people, and young stem-cell-derived tissues became old by every single hallmark.
This drug not only removes chronic inflammation, it stimulates regeneration and repair at the same time.
The data is transformed by biologically arbitrary weights that exist only to create a simplified trajectory.
It's not really the number that matters, it's how you got to that number.
Key ideas
9What heterochronic parabiosis really shows
When old and young mice share circulation, old tissues get younger and young tissues age. But the setup adds confounders such as shared organs, exercise and environment, so the blood is not necessarily a magic signal.
Young blood is not the secret sauce
In blood exchange without suturing, old blood rapidly dominates and ages young mice. Beneficial factors in young blood also exist in old blood but cannot override the elevated age-and-pathology proteins.
Dilution alone drives rejuvenation
You do not need young blood at all. Simply diluting old plasma produces rejuvenation, a finding that fueled the growth of plasma-exchange clinics.
Aging in four days
Fresh iPSC-derived human liver and fat tissue aged by every hallmark within four days of exposure to old human serum. Conboy argues this shows aging is driven by the systemic environment, not just elapsed time.
Hundreds of factors, no silver bullet
Old blood contains hundreds of drivers of aging, so a single-target approach is unlikely to work. In organ-chip screening, dilution of old serum worked best and rapamycin did not.
Chronic inflammation and a dual-action therapeutic
The field increasingly agrees chronic inflammation is a key driver of aging. One Generation is designed to both neutralize age-elevated factors and boost tissue stem-cell repair at once.
Why epigenetic clocks fall short
Conboy argues clocks use elastic-net regression that treats what happens between young and old as unimportant, replacing it with a simplified line built on biologically arbitrary weights.
System Age measures instability, not a model
Instead of fitting a trajectory, Generation Lab measures rising variability, or noise, in homeostatically vital genes whose average methylation stays constant with age. It is a direct quantification rather than a prediction.
Men and women age differently
Epigenetic instability appears earlier in heart-related genes in men, while women's aging trajectory shifts sharply around menopause, affecting bone, brain and muscle.
Practical takeaways
6- 1
Only lifestyle is proven so far 34:00
Both scientists agree that, to date, only diet, exercise, sleep and social connection are proven to support healthier aging in people.
- 2
Your environment shapes your epigenome 1:00:00
A large share of epigenetic change is driven by stress, toxins and environment, much of it reversible, so daily choices matter.
- 3
Look at which system is aging 1:04:30
Rather than fixating on one biological-age number, focus on which body system is aging fastest and what is driving it.
- 4
Small changes can reverse exposure damage 1:05:30
One co-founder's elevated lung age from woodworking dust reversed after three months of using an air filter, showing that identifying and removing an exposure can help.
- 5
Be skeptical of single-number clocks 50:30
Repeat consumer epigenetic tests can swing by the equivalent of years on the same day, so treat any single biological-age number with caution.
- 6
Early signals enable early action 1:06:00
Catching a fast-aging system early, before proteins or symptoms change, creates a window to act with lifestyle or clinician-guided steps.
Topics & chapters
13Introduction and Generation Lab
Kaeberlein introduces co-founders Irina Conboy and Alina Su and the company's origins.
Alina's path into longevity
A grandfather's early death and a parabiosis slide in class sparked Alina's mission and her pursuit of Conboy as a mentor.
Leaving academia
Conboy describes fully transitioning from a Berkeley professorship to lead Generation Lab.
Heterochronic parabiosis
A tour through what shared circulation does to old and young tissues and its confounders.
The young blood myth
Blood exchange without suturing shows old blood dominates and ages young animals.
Plasma dilution
Diluting old plasma alone drives rejuvenation, spurring plasma-exchange clinics.
Organ chips age in four days
Old serum ages young human tissues fast, reframing what aging is.
The rapamycin debate
Kaeberlein and Conboy discuss absolute versus percent lifespan effects and translatability.
Inflammation and One Generation
Chronic inflammation as a driver and the dual-action therapeutic built by rational design.
The self-experiment
Co-founders across three decades self-inject weekly and track many biomarkers.
Why clocks fail
Conboy's critique of elastic-net clocks and biologically arbitrary weights.
System Age and the 21 systems
Measuring epigenetic instability of vital genes and mapping it to organ systems.
Testing, validation and actionability
At-home testing, reproducibility, case-by-case interventions and next steps.