Huberman and Fajgenbaum Sound the Alarm on America’s Forgotten Anti-Aging Drugs

Highlights

• Andrew Huberman and David Fajgenbaum explain how familiar, widely used medicines influence inflammatory and metabolic pathways that shape long-term health and aging.
• Their conversation highlights how everyday drugs, sleep patterns, and chronic stress all act on shared immune and cellular repair mechanisms that affect healthspan.

Most conversations about longevity focus on futuristic drugs, high-tech therapies, or experimental biohacks. Yet, in a recent episode of the Huberman Lab podcast, physician-scientist David Fajgenbaum described a very different view of aging science. He explained that many of the tools that influence how long we stay healthy already exist in familiar pharmacies, hiding in plain sight.

Fajgenbaum built his scientific career after nearly losing his life to a rare immune disorder. That experience pushed him to look beyond experimental treatments and to ask whether existing drugs could be repurposed to target overlooked biological pathways. He joined Dr. Andrew Huberman to explain how many everyday medicines interact with the inflammatory, metabolic, and immune signals that shape healthspan. His central point is that medicines already in circulation influence the same biology that drives aging, while many of their broader effects remain unstudied.

The Hidden Influence of Everyday Drugs on Aging Biology

Huberman and Fajgenbaum highlight several medications whose biological effects extend far beyond their original indications. Fajgenbaum notes that aspirin alters inflammatory signaling involved in cardiovascular and metabolic stress. He explains that tadalafil improves vascular function in both adults and children with pulmonary hypertension by supporting nitric oxide pathways, which help blood vessels relax and carry oxygen more efficiently. He also points to lithium, which interacts with neuronal signaling networks involved in mood and memory, making it a candidate for slowing age-related cognitive decline.

Both speakers emphasize that these drugs reach pathways that regulate inflammation, immune tone, metabolic stress, and cellular repair. When these systems function more effectively, tissues maintain structure and performance for longer periods. As Fajgenbaum explains, this is why a single drug can influence both a disease state and features of aging biology.

Inflammation Control Plays a Major Role in Long-Term Health

Huberman asks Fajgenbaum to expand on inflammation as a central driver of aging, and the examples he provides show how strongly inflammatory pathways influence long-term health. Fajgenbaum describes how colchicine, an anti-inflammatory drug traditionally used for gout, reduces inflammatory activity inside arterial plaques, referring to the fatty buildups that form inside arteries and raise the risk of heart attack.

Clinical research strengthens this point. Large trials such as COLCOT and LoDoCo2 followed thousands of patients and found that low-dose colchicine reduced the incidence of major cardiovascular events. These findings align with colchicine’s ability to suppress inflammatory activity within blood vessels and prevent plaque destabilization, a major trigger for heart attacks.

He also explains that TNF-blocking therapy — drugs that neutralize tumor necrosis factor, a potent inflammatory molecule — protects children with DADA2, a rare genetic immune disorder marked by severe vascular inflammation and early strokes. Aspirin similarly reduces immune signals associated with cardiovascular risk and certain cancer outcomes.

These examples show that lowering chronic inflammatory pressure supports vascular stability, metabolic control, and the body’s ability to repair everyday damage.

Sleep, Stress, and Recovery Shape the Pace of Aging

Huberman goes on to bring up lifestyle habits, and Fajgenbaum outlines how sleep and stress modulate the immune pathways involved in aging. He describes animal studies showing that severe sleep deprivation triggers an inflammatory surge that can overwhelm the body.

Human research mirrors this pattern. Controlled sleep-restriction studies consistently show increases in inflammatory molecules after even modest sleep loss. Participants often exhibit higher levels of IL-6, TNF-α, and C-reactive protein, which are key markers of systemic inflammation and contributors to long-term disease risk. These responses appear within days, demonstrating how quickly sleep disruption affects immune regulation.

Fajgenbaum also discusses how prolonged psychological stress alters immune behavior in people. He notes that individuals under sustained pressure often show elevated inflammatory markers and reduced resilience, especially when stress persists chronically. Huberman reinforces that consistent sleep and controlled stress help maintain immune stability, which in turn influences long-term health.

Together, their observations show that daily behaviors influence the same biological pathways targeted by many repurposed drugs.

Economic Barriers Limit Research on Generic Drugs With Longevity Potential

Even though many medications interact with aging pathways, only a small fraction receive significant research attention. Once a drug becomes generic, financial incentives for conducting large clinical trials disappear. Without funding, promising findings remain scattered and unused.

“There’s 4,000 FDA-approved drugs that are approved for about 4,000 diseases. But we know from laboratory work and also from clinical trials that many of those drugs can be used in more diseases. But unfortunately, the system really isn’t set up to find new uses for old medicines,” states Fajgenbaum.

Lidocaine illustrates this challenge. It is a standard anesthetic, yet in a major clinical trial, applying lidocaine around a tumor before breast cancer surgery reduced mortality in the years that followed. Despite this result, the discovery gained little visibility because the drug is inexpensive and off-patent.

The lack of financial support leaves many promising drug effects undocumented, limiting what researchers can learn about their potential role in healthier aging.

AI Tools Help Identify Overlooked Medicines That Support Healthspan

To address this gap, Fajgenbaum and his team at Every Cure are building a biomedical map that connects drugs to the molecular pathways they influence. The system integrates information from clinical trials, mechanistic studies, patient reports, and real-world medical data. Its goal is to identify overlooked matches between existing medicines and the biological processes they affect.

Huberman notes that combining this type of map with personal biomarkers could eventually help clinicians design individualized health strategies. Instead of relying solely on new drugs, physicians could evaluate how well-studied medications align with a person’s molecular profile.

By mapping these connections, researchers gain a clearer view of which existing medicines may offer real, immediate value for improving healthspan.

Targeted Interventions Show That Aging Biology Can Shift

Fajgenbaum’s medical history demonstrates how strongly the body can recover when the right pathway is targeted. After multiple life-threatening episodes of Castleman disease, he identified the immune signal driving the disorder and treated it directly. His recovery shows that biological decline is not fixed. Cellular systems respond quickly when the correct mechanisms are supported.

Aging follows a similar pattern. It reflects ongoing adjustments in inflammation, metabolism, immunity, and repair. When these processes stay within a healthy operating range, the body maintains stability and resilience for longer periods.

Huberman and Fajgenbaum’s conversation points toward a meaningful insight. Many useful longevity tools already exist, and understanding them more deeply may offer one of the most accessible paths to a longer healthspan.