What if aging could actually be reversed? And why are investors putting money into companies trying to make it happen?

Dr. Karl Pfleger spent a decade at Google after earning his PhD in Computer Science at Stanford. Today, he's an aging biotech investor who has backed around 30 companies working on one of the biggest challenges in medicine: reversing biological aging.

His investment philosophy is unusually specific. He's interested in therapies that repair the molecular damage associated with aging, rather than simply slowing down the aging process.

In this episode of Return on Health, Niko Hems and Miguel Medina speak with Karl about where the aging biotech industry is heading, which scientific breakthroughs could make the biggest difference, and what it would actually take to demonstrate that a therapy reverses aspects of human aging.

We discuss:

→ Why Karl invests in age-reversal therapies rather than interventions that merely slow aging

→ What makes an aging biotech startup worth investing in

→ Senolytics, stem cells, and epigenetic partial reprogramming

→ Why biological age clocks aren't sufficient proof that an intervention works

→ The regulatory challenges facing aging biotech companies

→ Why immune system rejuvenation and thymus regeneration deserve more attention

→ Whether people alive today could live to 150

→ Why Karl thinks rapamycin, GLP-1 drugs, and single-intervention lifespan studies receive too much attention

→ His personal longevity routine, from exercise and nutrition to supplements and sleep medication

→ Why he believes healthcare systematically underestimates the harm of doing nothing

Karl also explains why he thinks aging research remains severely underfunded compared with cancer research, and what needs to change to bring more therapies into clinical practice.

Chapters

00:00 Why invest in reversing aging?
03:44 From Stanford and Google to aging biotech
08:20 What would a world without biological aging look like?
12:28 Can we reverse aging within our lifetimes?
19:20 The ethics of radical life extension
25:03 How Karl evaluates aging biotech investments
31:10 What makes a biotech startup investable?
33:12 The evidence investors want to see
38:08 How do we prove an aging therapy works?
44:03 Aging versus lifestyle-related disease
50:01 The potential of thymus rejuvenation
50:38 Karl's personal longevity routine
56:42 Rapid-fire questions
57:11 The most promising hallmark of aging
58:29 What's overhyped in longevity?
59:45 The experiments Karl would fund
1:03:29 What needs to change in healthcare?

About our guest

Dr. Karl Pfleger is an aging biotech investor, former Google engineer, and Stanford-trained computer scientist. He founded AgingBiotech.info, a resource tracking companies and developments across the aging biotechnology industry.

Learn more: https://agingbiotech.info

About Return on Health

Hosted by Niko Hems and Miguel Medina, Return on Health brings researchers, physicians, entrepreneurs, and critical thinkers together to question assumptions about health, medicine, and longevity.

Subscribe for conversations about the science, business, and future of human health.

#Longevity #AgingResearch #Biotech #AgeReversal #KarlPfleger

Can chronic infections drive chronic disease?

Dr. Richard Horowitz has spent more than four decades treating patients with complex chronic illness, including Lyme disease, long COVID, chronic fatigue, neurological symptoms and multi-system disease.

His central argument is controversial: many chronic illnesses cannot be explained by a single diagnosis or a single cause.Instead, Horowitz proposes a framework of interacting factors including persistent infections, environmental toxins, microbiome dysfunction, intestinal permeability, nutrient deficiencies, sleep, mitochondrial dysfunction, dysautonomia and chronic inflammation.

But how much of this is actually proven? And where does association end and causation begin?

In this episode of Return on Health, we push Dr. Horowitz on exactly those questions.

We discuss

• Why some patients remain symptomatic after Lyme disease treatment

• The debate around chronic Lyme disease and post-treatment Lyme disease syndrome

• Borrelia, Bartonella and Babesia

• Biofilms and bacterial persister cells

• His 16-factor MSIDS framework for chronic illness

• Mold exposure, mycotoxin testing and its clinical limitations

• Heavy metals, microbiome dysfunction and intestinal permeability

• Dysautonomia, POTS and mast cell activation

• Why a positive test does not necessarily mean something is causing symptoms

• How Horowitz decides which potential drivers to treat first

• His dapsone combination protocol for chronic Lyme disease

• The risks and required screening before dapsone treatment

• Why observational results and clinical experience are not enough

• The need for randomized controlled trials

• Lyme disease, neuroinflammation and Alzheimer's disease

• His published case involving P-tau217 and other Alzheimer's biomarkers

• Why improving a biomarker is different from proving an effect on dementia

• What conventional medicine may be missing, and where alternative approaches can go too far

Horowitz himself acknowledges one of the central limitations: much of this work still needs stronger evidence capable of moving from association toward causation.

One example is mold testing. A patient may test positive for mycotoxin exposure, but that alone cannot establish that mold is responsible for their symptoms.

The same question comes up when we discuss Alzheimer's biomarkers. Horowitz presents cases in which P-tau217 and other biomarkers changed after treatment, while we challenge what can actually be concluded from a surrogate biomarker without clinical outcome data.

About Dr. Richard Horowitz

Dr. Richard Horowitz is an internal medicine physician focused on Lyme disease and complex chronic illness. He has treated more than 13,000 patients and developed the MSIDS framework discussed throughout this episode.

His new book, Ending Chronic Illness: A Revolutionary New Program to Reverse Inflammation and Heal Persistent Disease, will be released on October 13, 2026.

Richard Horowitz

Website: https://cangetbetter.com/

New book, Ending Chronic Illness: https://cangetbetter.com/Book

Website: https://www.endingchronicillness.com/

Return on Health

Website: https://returnonhealth.de/Watch and listen to all episodes of Return on Health on YouTube, Spotify and Apple Podcasts.

Return on Health is hosted by Niko Hems and Miguel Medina Stanivukovic.

We speak with researchers, physicians, founders and skeptics about longevity, prevention and the future of health, with one rule: strong claims deserve strong questions.

Important

This episode discusses experimental and controversial diagnostic and treatment approaches. The views and clinical claims expressed by guests do not constitute medical advice or endorsement by Return on Health. Some approaches discussed are outside established clinical guidelines and require substantially stronger evidence.

What if the most promising drug for slowing aging already exists.. but we still do not know whether healthy humans should take it?

Dr. Matt Kaeberlein is one of the leading scientists studying the biology of aging. His work has focused on mTOR, rapamycin, cellular aging and the mechanisms that may allow us to extend healthy lifespan.

In this episode of Return on Health, hosts Niko Hems and Miguel Medina challenge Matt on how far longevity science has actually come.

They discuss what aging really is, whether the Hallmarks of Aging are causes or consequences, and why changing one pathway or biomarker often fails to produce the health outcome we expect.

The conversation then turns to rapamycin. Matt explains why it has some of the strongest preclinical evidence of any potential longevity intervention, why it has extended lifespan across multiple animal models, what decades of use in transplant medicine tell us about safety, and why the doses used for longevity are very different.

They also discuss the biggest unanswered question: does any of this translate meaningfully to healthy humans?

Matt explains why he personally uses rapamycin periodically, what he thinks about emerging evidence in chronic inflammation and ME/CFS, and why its effects on mTOR do not necessarily mean it will accelerate age-related muscle loss.

The episode also takes on some of the biggest claims in longevity.

Matt argues that the human evidence behind NAD supplementation remains weak, warns against stacking large numbers of supplements with uncertain effects, and explains why many consumer-facing biological age tests are currently far less useful than their marketing suggests.

They also discuss longevity escape velocity, whether AI could accelerate aging research, rapamycin vs GLP-1 receptor agonists vs metformin, and why companion dogs may be one of the most useful models for understanding human aging.

━━━━ 👤 ABOUT THE GUEST ━━━━

Matt Kaeberlein, PhD is a scientist focused on the biological mechanisms of aging and interventions that may extend healthspan.

His research has covered mTOR signaling, rapamycin, cellular aging and lifespan regulation. He is also a co-founder of the Dog Aging Project, which studies how genetics, environment and interventions influence aging in companion dogs.

━━━━ 🎙️ ABOUT THE HOSTS ━━━━

Niko Hems is Head of Strategy & Medical Communications at YEARS, a preventive medicine company using longitudinal and multi-modal health data to make prevention more personalized and data-driven.

Miguel Medina is co-host of Return on Health, a podcast built around a simple idea: a system produces the outcomes it is incentivized to produce — so better health outcomes require better incentives.

━━━━ 💡 KEY QUESTIONS ANSWERED ━━━━

• What actually causes biological aging?
• Are the Hallmarks of Aging incomplete?
• Why is mTOR so important for longevity?
• Can rapamycin really slow aging?
• How strong is the human evidence?
• What are the main risks and side effects?
• Does rapamycin interfere with muscle growth?
• Could it help with chronic inflammation or ME/CFS?
• Is there strong evidence for NAD supplements?
• Are biological age tests useful yet?
• Is longevity escape velocity scientifically realistic?
• Rapamycin vs GLP-1s vs metformin: where is the strongest evidence?
• Why could studying dogs help us understand human aging?

━━━━━━━━━━━━━━━

Connect with Matt:

Dog Aging Project: https://dogagingproject.org/