Peter Ottsjö frames Dr. Matt Kaeberlein as “one of the world's most respected aging scientists,” tracing his training in Leonard Guarente’s lab at MIT, prominence with rapamycin, the Dog Aging Project, and co-founding Ora Biomedical (WormBot) and Optispan. He notes fellowships, >250 papers, and a reputation for honesty about promise and limits.

Peter surfaces an old photo (see below) from the “mythological Guarente lab,” asking for Matt’s reaction to that era with David Sinclair and Brian Kennedy. Matt recalls shifting from structural biology to aging after a talk by Leonard Guarente on yeast rDNA and aging, describing an exhilarating phase of discovery when new longevity genes emerged weekly.

Matt sketches a non-linear path: a startup with Pete Estep (Longenity) on human aging clocks; a return to the Pacific Northwest; a postdoc with Stanley Fields at the University of Washington; and a decades-long collaboration and friendship with Brian Kennedy producing “more than 100 papers.” He emphasizes conserved aging mechanisms across species.

Seeking unbiased discovery beyond sirtuins and insulin signaling, Matt and Brian ran a yeast lifespan screen; deletion of TOR1 strongly extended lifespan. Literature led Matt to David Sabatini’s mTOR biochemistry and the drug rapamycin/sirolimus, prompting tests that showed lifespan extension in yeast (2006), followed by mice via the Interventions Testing Program.

Matt highlights a “happy accident” in the Interventions Testing Program: rapamycin started at ~20-month-old mice (≈ 60 year old human) still robustly extended lifespan. He lists other late-life mouse interventions with evidence: Acarbose, Canagliflozin, 17-alpha-estradiol.

Matt explains the Dog Aging Project’s primary observational, longitudinal design in companion dogs, with two goals: understand genetic/environmental factors shaping healthspan/lifespan and “do something about it,” plus an indirect goal to inform human aging. Dogs share human environments, have diverse genetics, and age 7–10× faster, enabling practical timelines.

He recounts origins (2014–2015), early media sparks, and building toward a rapamycin clinical trial. COVID-19 forced a pivot to expand the longitudinal cohort to 50,000+. A 2023 NIH renewal was not funded; philanthropic support kept lights on. The rapamycin clinical trial has since been re-funded; a new longitudinal grant is being submitted.

From pilots: rapamycin appears safe in dogs with hints of improved heart function and activity; the large trial remains blinded. Observationally, once-daily feeding correlates with lower risk across seven age-related conditions; physical activity strongly predicts lower dementia risk; sterilization status matters; intriguingly, larger body size doesn’t raise dementia risk in dogs. Here you can find everything published so far in the Dog Aging Project.

Patrick mentions Cryopets; Matt distinguishes psychologies: drug/supplement trials vs. cryopreservation interest, while supporting personal freedom with responsible frameworks. Peter notes Cryopets’ waitlist versus humans, suggesting cultural gaps: people align around pet aging even if not human aging. Matt sees projects like DAP as public education on aging as a modifiable process.

Matt sets expectations: no definitive human longevity data yet; He used rapamycin (6 mg weekly ×10 weeks) for adhesive capsulitis (“frozen shoulder”) with rapid pain relief and restored function; he now cycles it intermittently, emphasizing risk-reward and uncertainty.

On label expansion: none he knows pursuing rapamycin expansions in humans; novel mTOR-pathway drugs are in development but costly. He critiques small safety-framed studies that don’t answer efficacy and urges NIH leadership to bridge academia and for-profit gaps with rigorous trials that current incentives neglect.

Peter questions NIH priorities; Matt counters that high-level policymakers may lack aging-science expertise and the field has “sabotaged itself” via irresponsible actors. He praises the Alliance for Longevity Initiatives (A4LI), Dylan Livingston, and a bipartisan Longevity Science Caucus.

Matt supports expanded right-to-try; he testified in Montana and aided representative Ken Bogner on language. He wants responsible regulatory frameworks to enable access while collecting useful data, contrasting with offshore clinics and unregulated manufacturing (e.g., stem cells, exosomes, peptides) that risk safety issues and yield little evaluable evidence.

Concerned that the Hallmarks paradigm narrowed inquiry, Matt co-founded Ora Biomedical to run massive, unbiased intervention screens in C. elegans via WormBot (robotics + AI imaging). He argues we’ve barely touched overexpression/essential-gene space; Ora has screened ~10,000+ interventions, finding combo synergies and a candidate mTOR inhibitor ~2× rapamycin potency (early).

He’s cautious on AI for novel interventions because models trained on rapamycin/metformin “predict things that look like” them; a million-intervention dataset would be transformative training data. He is more optimistic on biomarkers, multi-omics integration, digital-twin ideas, and especially LLM-assisted clinical practice to synthesize diagnostics and scale proactive care.

Matt positions Optispan as a healthcare technology company with clinical programs and a podcast, aiming to enable science-based proactive care. They built clinics first to learn friction points, now developing computational infrastructure for “best in class health span medicine” and an “80-20” tier for broader access, avoiding direct-to-consumer paths that can incentivize weak practices.

He critiques DTC diagnostics without integration and providers recommending epigenetic “biological age” tests lacking precision, accuracy, and actionability. He is bullish on epigenetics as research tools and for multi-cancer detection, but condemns dishonest claims and sloppy communication by scientists and clinics alike.

Matt tried therapeutic plasma exchange (TPE) via Circulate Health (Matt is on their scientific advisory board), citing FDA-approved safety for other indications, plausible dilution of metals/microplastics, and intriguing cognitive data. His personal outcomes: no felt boost; lipids dipped transiently; microplastics assay ambiguous (tubing could add). He remains cautiously positive for certain use cases.

Peter references a Buck and Circulate study; Matt corrects common phrasing: it showed methylation changes “consistent with reduced mortality,” not measurement of biological age. He warns that such sloppiness harms field credibility and contrasts with standards in areas like cancer research.

Closing with book picks, Matt recommends Outlive by Peter Attia for proactive health communication, Stephen Hawking’s A Brief History of Time for scientific curiosity, The Man Who Saw Seconds by Alexander Boldizar, and Mountainside by his wife Tammi Kaeberlein (plus a forthcoming Alaska-based novel).