Emerging research suggests that lifestyle factors including exercise, nutrition, and heat exposure may influence the cellular pathways that drive aging.
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Can human aging be slowed or even reversed? On a recent episode of the Huberman Lab podcast, Stanford neuroscientist Dr. Andrew Huberman sat down with Harvard geneticist Dr. David Sinclair to unpack what the science says about the mechanisms of slowing aging and interventions that may help us stay healthier longer. The discussion covered many topics, from epigenetics and mitochondria to caloric restriction, exercise, sauna use and experimental approaches to cellular “rejuvenation.”
Here are six key takeaways from the conversation and what they mean for patients.
Aging may be driven by cellular information loss, not just wear and tear
Most of us learned that aging results from the slow accumulation of damage in our cells until they eventually fail. Sinclair argues that this is only part of the story.
Think of the DNA sequence as the cell’s hardware. This remains relatively stable over a lifetime. What becomes disorganized is the epigenetic “software” that regulates gene expression. The epigenome encompasses the chemical and structural marks that tell cells which genes to turn on and off. As this software degrades, cells lose their identity and function even when their underlying DNA remains intact.
He proposes the “information theory of aging,” which frames aging as a problem of epigenetic information loss. A 2025 human tissue study found that distinct epigenetic signatures, specifically DNA methylation patterns, become increasingly disordered with age across multiple organs. In essence, gene-regulatory networks grow noisier and less precise, reducing the amount of reliable biological information a cell can use to maintain its function.
Sinclair’s own experimental work supports this hypothesis in animals. In a 2020 Nature study, partially reprogramming retinal cells in mice restored youthful gene expression and reversed age-related vision loss. While early and limited to a specific organ, the findings suggest that some age-related epigenetic changes may be reversible.
Mitochondrial decline is a central feature of aging biology
Another major theme of the discussion was the role of mitochondria—the tiny organelles responsible for generating cellular energy. As we age, mitochondria tend to produce less energy, generate more reactive oxygen species and show impaired quality-control mechanisms. Reviews across species link mitochondrial dysfunction to muscle loss, neurodegeneration, cardiovascular disease, and other age-related conditions.
One of the key regulators of these mitochondrial processes is NAD⁺, a coenzyme essential for energy production and DNA repair. In a 2013 Cell paper, Ana Gomes and colleagues in Sinclair’s lab demonstrated that NAD⁺ levels fall with age in mice, leading to impaired communication between the cell nucleus and mitochondria. Restoring NAD⁺ levels with precursors helped repair that signaling and improved mitochondrial function.
This line of work supports one of Sinclair’s core messages: keeping mitochondrial systems functioning—the biological power grid—may delay or reduce many age-related diseases.
While NAD⁺ boostering supplements such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) can reliably raise NAD⁺ levels in humans and modestly improve some cardiometabolic markers, no clinical study has yet shown that increasing NAD⁺ slows aging or extends lifespan in people. Still, the underlying biology, combined with promising animal data, continues to drive interest in NAD⁺ as a potential node for future longevity interventions.
Caloric restriction shows promise in slowing aging but is not a magic bullet
Caloric restriction and intermittent fasting often trend on social media as longevity hacks. While some claims of their benefits are overstated, the underlying science is compelling.
In worms, flies, and rodents, chronic caloric restriction without malnutrition reliably extends lifespan and delays multiple age-related diseases. Much of this benefit appears to involve nutrient-sensing pathways such as mTOR, AMPK, and the sirtuins. These pathways act as metabolic “fuel gauges,” detecting how much energy is available and deciding whether cells should grow or shift into repair mode.
When energy is scarce, these pathways favor increased autophagy (cellular cleanup), enhanced stress resistance and improved mitochondrial efficiency, all of which support healthier aging.
The challenge is that we do not have 40-year human trials. But we do have high-quality human data that lends some support for health improvements with calorie restriction. In the CALERIE trial, healthy, non-obese adults were randomized to about two years of modest caloric restriction (12% less) or usual diet. Those in the calorie restriction group showed meaningful reductions in blood pressure, LDL cholesterol, inflammatory markers and other cardiometabolic risk factors linked to aging.
The takeaway is not that patients should starve themselves. The issue is that frequent overeating keeps nutrient-sensing pathways permanently in growth mode. This suppresses cellular repair systems, accelerates molecular damage and increases long-term disease risk.
Modest, sustainable periods of reduced intake, whether through mild calorie restriction or structured fasting give cells time to repair and recalibrate metabolism. These approaches likely improve health. But whether they extend human lifespan remains unknown.
Exercise is the closest thing we have to a longevity drug for slowing aging
If there is one intervention nearly all longevity researchers agree on, it is exercise. Sinclair calls it “non-negotiable,” and the evidence is overwhelming.
A landmark Taiwanese cohort study of more than 400,000 adults found that as little as 15 minutes of moderate exercise per day was associated with a 14% reduction in all-cause mortality and roughly three extra years of life expectancy compared with inactivity. Additional daily activity alo conferred greater benefit.
Large, pooled analysis of more than 650,000 participants in the U.S. and Europe show similar results. Meeting standard guidelines of about 150 minutes per week of moderate activity is associated with 3 to 4.5 additional years of life expectancy. Higher levels of activity continue to show benefit with no clear signal of harm.
Mechanistically, exercise acts as a controlled biological stressor. It stimulates new mitochondria, improves insulin sensitivity, reduces chronic inflammation, and activates many of the same pathways influenced by caloric restriction.
Heat, cold, and other forms of “good stress” may support slowing aging
Sinclair and Huberman have also discussed the concept of hormesis: the idea that short, tolerable bursts of stress trigger adaptive responses that make the organism more resilient.
The strongest human data involve heat. In a 20-year study of more than 2,000 middle-aged Finnish men, those who used a sauna 4–7 times per week had significantly lower risks of sudden cardiac death, fatal coronary heart disease and all-cause mortality than those who used a sauna once per week. While not proof of causation, the results are striking and biologically plausible.
Cold-exposure data are more limited, but small human studies and animal work show increased brown fat activation, improved insulin sensitivity and mitochondrial remodeling. Used safely and with medical guidance, heat and cold exposure may be practical tools for improving metabolic and mitochondrial health.
What research on slowing aging means for patients
None of this means we have “solved” aging. There is no pill that reliably extends human lifespan and attention. Attention grabbing interventions like NAD⁺ boosters or epigenetic reprogramming remain experimental.
But taken together, this research points toward a coherent framework linking cellular mechanisms of aging with actionable interventions, in particular lifestyle and environmental factors. For clinicians, the practical message is familiar: interventions that improve metabolic, mitochondrial and epigenetic health likely offer the greatest leverage to make people healthier and extend lifespan.
That means reinforcing fundamentals such as nutrition, movement, sleep and stress management, while maintaining cautious optimism about emerging therapies that target aging biology more directly.
Ultimately, we are not on the verge of immortality. But if the science on slowing aging highlighted in Huberman-Sinclair conversations continue to hold up, we may help more people reach advanced age with better vision, stronger muscles, healthier brains and greater independence.
