A Longevity Physician on Stress, Meaning, and How We Age
By Dr. Lienna Wilson, Licensed Psychologist | Vagus Vitality
Most conversations about longevity start with a list: the right labs, the right supplements, maybe a prescription or two. Dr. Sajad Zalzala has spent years at the leading edge of that world, as a co-founder of the longevity telehealth company AgelessRx and an investigator on PEARL, the longest clinical study of rapamycin for healthy aging at the time it was published (Moel et al., 2025). Yet when he talks about what actually shapes how people age, he starts somewhere less expected: with stress, meaning, and whether someone feels steady enough in their own life to follow through on their care.
Dr. Zalzala now leads Optional Aging, a physician-led approach to understanding the interconnected factors that shape healthspan, the years we spend in good health. I asked him how nervous system health fits into longevity medicine, what terms like biological age and heart rate variability can and can’t tell us, and where he would start if someone wanted to support healthy aging today. Along the way, he offered something the longevity field could use more of: a careful habit of matching the strength of a claim to the strength of the evidence.
Foundations, Not Just Drivers
Dr. Zalzala’s framework grew out of a pattern he kept seeing in clinical practice. “People could understand what to do for their health and still struggle to do it when they were exhausted, overwhelmed, or living in a constant state of threat,” he says. That observation shaped how he built Optional Aging.
The framework looks at seven interconnected areas of health, including sleep, metabolism, hormones, and inflammation. But Dr. Zalzala also pays attention to what sits underneath them. “Stress regulation, mindset, relationships, meaning, and, for people who value it, spirituality belong in that conversation,” he says.
He made that distinction on purpose. “It would have been easy to put stress and nutrition on a list of ‘drivers,’ alongside sleep, metabolism, and inflammation,” he explains. “Instead, I treat them as foundations because they influence multiple drivers at once.” Keeping those categories separate helps him ask better questions: “Which areas of health are showing signs of strain, and which underlying habits or pressures may be affecting them?” It also keeps him from implying “that every health concern has the same cause or can be solved by stress management alone.”
In his view, these foundations reinforce one another in both directions. “A sense of purpose or spiritual practice may help someone navigate stress,” he says. “Feeling safer and less overwhelmed may make it easier to sleep, move, connect with others, and follow through on care.” The reverse holds too: “Persistent poor sleep or physical symptoms can make emotional resilience much harder.” Throughout, he is careful about how this lands with patients. “I try to understand the whole situation without suggesting that someone’s illness is a failure of mindset or faith.”
Stress and the Ability to Recover
When it comes to chronic stress and aging, Dr. Zalzala points to how many systems it touches at once. “Chronic stress can affect sleep, hormone levels, metabolic health, and the choices people are able to make day to day,” he says.
Rather than defining a well-regulated nervous system as one that is always calm, he thinks of regulation as flexibility: “the ability to respond to a challenge and then recover, rather than remaining on alert long after the immediate demand has passed.” That framing echoes one of the most influential ideas in stress research. Neuroscientist Bruce McEwen described a healthy stress response as one that switches on to meet a challenge and then shuts off once the threat has passed. When that cycle breaks down, whether through stress that keeps coming, a body that never adapts to it, or a response that fails to shut off afterward, the result is cumulative wear and tear that he called allostatic load, which over time can contribute to disease (McEwen, 1998). Recovery, in other words, matters as much as the stress itself.
What “Biological Age” Can and Can’t Tell You
Biological age has become one of the most talked-about ideas in longevity, and Dr. Zalzala uses it with care. “‘Biological age’ is a useful way to start a conversation about how people of the same chronological age can have very different health and function,” he says. “It is not a single clinical measurement that tells me exactly how old someone’s body is.”
He is just as measured about aging clocks, the lab tests that estimate biological age from markers such as DNA methylation. “Aging clocks are interesting research tools, but I would be cautious about treating a change in one clock as proof that an intervention reversed aging, or even improved overall health.” Leading researchers in the field have raised similar concerns, noting that there is not yet a consensus on what makes an aging biomarker reliable enough for clinical use (Moqri et al., 2023).
In practice, he focuses on changes that matter to the person and that he can interpret reliably: “sleep quality, mitochondrial function, metabolic measures, and how well they function in daily life.” Inflammatory markers have a place, but a narrow one. “They are affected by many things and are not a general-purpose ‘stress score,’” he says. “If someone feels more resilient, sleeps better, and has improving metabolic health over time, that is meaningful to me clinically even if I cannot translate it into a number of years of biological age.”
That thinking is behind his AgeScore 360 assessment, which brings together symptoms, function, health habits, and relevant biomarkers “to identify what deserves attention.” He is clear about what the number is for. “The ‘score’ is a way to organize a useful conversation and track priorities over time, not a claim that I can measure someone’s exact biological age or prove that a particular intervention has reversed it.” He is also optimistic about where it could go. He believes the assessment is likely directionally correct, and that it might one day be validated or refined into a more precise measure of how someone’s biological function compares to their chronological age.
Reading Heart Rate Variability in Context
Heart rate variability, or HRV, is the natural variation in time between heartbeats, and it has become one of the most popular numbers on wearable devices. Dr. Zalzala sees real value in it when it is read in context. “The vagus nerve is an important part of the communication between the brain and body,” he says. “Heart rate variability can provide a window into aspects of how the heart responds to autonomic signals.” A person’s HRV trend, he adds, “may sometimes be useful alongside their sleep, symptoms, training load, illness, medications, and other context.”
Where he draws the line is in how a single app reading gets interpreted. “I would avoid calling a wearable HRV score a direct measurement of someone’s overall ‘vagal tone,’” he says. “HRV changes with breathing, age, fitness, medication, illness, and how and when it is measured.” He also notes that it “seems to be heavily influenced by genetics and other factors that may be out of our control.”
That is a point about measurement rather than about the value of HRV itself. In research, HRV is one of the best-established ways to estimate the vagus nerve’s influence on the heart. Researchers also stress that how and when it is recorded matters, since values from 24-hour, short, and ultra-short recordings are not interchangeable (Shaffer & Ginsberg, 2017).
For Dr. Zalzala, the takeaway is practical. “A low reading on one morning does not diagnose nervous system dysfunction, and a higher reading does not prove someone is aging more slowly,” he says. “I’m more interested in whether the person is feeling and functioning better than in optimizing a number on an app.”
Lessons From the PEARL Trial
Dr. Zalzala brings a researcher’s perspective to longevity medications as well. He was an investigator on PEARL (Participatory Evaluation of Aging with Rapamycin for Longevity), a 48-week randomized, placebo-controlled trial of low-dose, intermittent rapamycin in generally healthy adults. Rapamycin has shown longevity-enhancing effects in mice, which is why it draws so much attention in longevity circles, but clinical data in humans remain limited (Moel et al., 2025).
“It was valuable to study the question in a randomized trial,” he says, and he is candid about the results. The primary outcome, visceral fat, did not improve significantly. “The study reported some encouraging secondary findings, particularly in women, that warrant further research,” he says, including gains in lean tissue mass among women taking the higher dose (Moel et al., 2025). Just as important is what the trial did not show. “It did not establish that rapamycin extends human lifespan or that pairing it with nervous system practices produces an added benefit.”
That experience reinforced a principle he carries into his practice: “Be curious about promising interventions, measure what they actually do, and keep the strength of the claim matched to the evidence.” In his framework, advanced interventions like rapamycin do have a role, but only after better-studied and more suitable options have been tried first. “Sleep, activity, nutrition, social connection, and ways to recover from stress deserve attention regardless of whether someone is considering a medication,” he says.
Supplements, Devices, and When to Look Further
Asked whether he recommends any supplements or devices for supporting vagal tone, Dr. Zalzala gives an answer that is refreshingly honest for the longevity space. “I don’t yet have a go-to supplement for vagal tone, other than maybe magnesium,” he says. “It would be great to be able to find one that consistently improves nervous system health.” That tentative “maybe” fits the research: a systematic review found the evidence suggestive of a benefit for anxiety in people already prone to it (Boyle et al., 2017).
He feels the same way about devices. “There seem to be several consumer devices on the market that seem promising, but I do not yet have enough experience with any individual one to make a strong or specific recommendation.”
More broadly, he believes “supplements should address a specific need rather than a vague promise to stimulate the vagus nerve.” He also offers an important caveat for anyone looking for a nervous system fix: “If someone has significant dizziness, fainting, palpitations, or other concerning symptoms, I would want an appropriate medical assessment instead of assuming the problem is stress.”
Where to Start: A Steadier Way to Meet Stress
If someone wanted to support healthy aging through their nervous system starting today, Dr. Zalzala’s suggestion is not a breathing technique or a gadget. It begins with how people relate to the pressures in their lives. “In my experience, some of the stress-related symptoms people describe are shaped by how they interpret and respond to the pressures in their lives,” he says. He is quick to add what that does not mean. “That doesn’t mean the pressures aren’t real, or that someone can think their way out of a medical condition. It means that finding a steadier way to meet stress may be an important part of their health.”
His starting point is a question: “What gives my life meaning, and how can I respond to this situation in a way that reflects it?” The answer looks different for everyone. “For one person, that may be faith or prayer; for another, family, service, or a sense of purpose,” he says. “That perspective can help put a stressful moment in context and guide the next action.”
There is research suggesting that purpose matters for health over the long run. In a study of nearly 7,000 U.S. adults over age 50, those with a stronger sense of life purpose had lower all-cause mortality during follow-up (Alimujiang et al., 2019). Because the study was observational, it cannot show that purpose itself causes longer life, but it fits the picture Dr. Zalzala describes.
“Breathing exercises and prayer can be useful,” he says, “but the deeper practice is developing a way to face life’s challenges that you can return to every day.”
For Dr. Zalzala, nervous system health is not one more longevity hack to add to the list. It is part of the foundation that makes everything else on the list possible: the sleep, the movement, the connection, and the follow-through. His approach also offers a useful model for reading any longevity claim: be curious, pay attention to what actually changes in a person’s life, and let the strength of the claim follow the evidence.
About Sajad Zalzala, MD
Dr. Zalzala is a longevity-focused physician and the founder of Optional Aging, a physician-led approach to understanding the interconnected factors that shape healthspan. He previously co-founded AgelessRx and was a co-investigator on the PEARL trial of rapamycin and healthy aging. His work focuses on helping people turn longevity science into practical, individualized steps for better health and optimizing health span. Learn more at optionalaging.com.
Note: Rapamycin (sirolimus) is a prescription medication that affects the immune system, and it is not FDA-approved for slowing aging or extending lifespan. Supplements, devices, and the other approaches discussed here are best considered with a qualified clinician as part of an individualized care plan. Nothing here is a substitute for medical care.
References
Alimujiang, A., Wiensch, A., Boss, J., Fleischer, N. L., Mondul, A. M., McLean, K., Mukherjee, B., & Pearce, C. L. (2019). Association between life purpose and mortality among US adults older than 50 years. JAMA Network Open, 2(5), e194270. https://doi.org/10.1001/jamanetworkopen.2019.4270
Boyle, N. B., Lawton, C., & Dye, L. (2017). The effects of magnesium supplementation on subjective anxiety and stress: A systematic review. Nutrients, 9(5), 429. https://doi.org/10.3390/nu9050429
McEwen, B. S. (1998). Protective and damaging effects of stress mediators. New England Journal of Medicine, 338(3), 171–179. https://doi.org/10.1056/NEJM199801153380307
Moel, M., Harinath, G., Lee, V., Nyquist, A., Morgan, S. L., Isman, A., & Zalzala, S. (2025). Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging, 17(4), 908–936. https://doi.org/10.18632/aging.206235
Moqri, M., Herzog, C., Poganik, J. R., Justice, J., Belsky, D. W., Higgins-Chen, A., ... & Gladyshev, V. N. (2023). Biomarkers of aging for the identification and evaluation of longevity interventions. Cell, 186(18), 3758–3775. https://doi.org/10.1016/j.cell.2023.08.003
Shaffer, F., & Ginsberg, J. P. (2017). An overview of heart rate variability metrics and norms. Frontiers in Public Health, 5, 258. https://doi.org/10.3389/fpubh.2017.00258