NRF-2 and the Cellular Mechanism of Self-Care
In college one summer I worked in a prestigious lab toiling over slides of rat neurons and dna/protein gels representing the complex inner workings of cellular processes. It was objectively fascinating and important, yet I failed to get any reward from the process. I grew up watching my father do the same work, but he delighted in this same process. I respected that. Science wasn’t just what he did; it was his religion.
I was taught to worship science from my earliest memories, even believing on some level that I was his ultimate experiment. He imagined the complexities of cellular mechanisms down to their chemical structures and derived so much satisfaction from his work. I can imagine his reward pathways lighting up when he dreamt up new theories for which drugs worked on which pathways in which type of cells. However, my heart yearned for truth, beauty, freedom, and love (queue that Moulin Rouge song), not just endless investigation. I ended up with panic attacks in a cocktail of shame, burnout, and imposter syndrome, and I lamented that I would never be like my father.
I eventually found my path from a biology degree to medical school and discovering psychiatry. Unlike laboratory research, sitting with patients and understanding the complexity of individuals did light up my dopamine pathways. Making recommendations and interventions in the moment felt quite satisfying. When to teach, when to push, when to empathize, when to reframe, and when to medicate — pulling the levers of a privileged therapeutic relationship. This continues to feel like a high stakes dance with a goal to help regulate a patient’s nervous system.
A Convergence of Paths
On a recent family trip I found myself paying more attention than usual to my aging father’s rambling monologues about his latest theory on rejuvenation. The rest of the family remained distracted with their eyes glazed over, much the same as always.
“Most diseases and aging itself are related to inflammation and oxidative stress. The body has a built-in mechanism to regulate oxidative stress that, when activated, could promote healing and rejuvenation from disease and aging. It’s called Nrf-2, a master control transcription factor that reduces the damage from oxidative stress in cells through multiple mechanisms.”
“Ok, so how do you activate Nrf-2?” I ask gamely.
“Well, there’s a few ways including eating broccoli and circumin and exercising, but it’s highly individual.”
“Wait, didn’t you use to say exercise was bad for you?” my sister asks sarcastically.
“That’s in the past,” my dad says, waving away his previous theories.
“Hold on, are you saying that the key to good health is a highly individualized regimen of self-care that everyone has to figure out for themselves? Hah, welcome to my world!” I say. I wondered if it was possible that the different paths that my father and I took in life had led us to the same conclusion.
The Science Behind Self-Care
A review of the literature shows that Nrf-2 has been shown to activate a protein called bdnf, which is tied to multiple mental health conditions. Nrf-2 activation has specifically been shown to increase antidepressant effects in rats through bdnf. I was surprised to learn that my father’s latest theories were quite relevant to mental health for my patients, not just physical health. I quickly reflect on how often I have encouraged patients to improve their self-care, not realizing that I was trying to activate their Nrf-2 master control gene.
After over a decade in practice I have learned that the act of self-care is critical and yet so elusive to my patients. My definition of self-care includes the regular habits and pursuits that improve our minds and bodies (that might include our work and our relationships). There are many barriers for a patient to engage in self-care including skepticism that it can help or not understanding that self-care can look different for everyone. For example, having alone time every day may be way more critical for an introvert than an extrovert. However, I now have a solid tool I can use when I encounter resistance to self-care in session: “Nrf-2! You have to activate the master control gene to heal yourself!” It’s almost comical how naming a transcription factor in a therapy session will raise an eyebrow.
Understanding Body Signals
Often, a barrier for patients to pursue self-care is not knowing what their body needs. The signals that normally tell us when something feels good or aversive can be disconnected and unanswered. Whether from trauma, neurodivergence, or just not wanting to pay attention, this disconnection can get in the way of healthy functioning (and likely lead to oxidative stress and inflammation) in both the mind and the body. I recalled my previous pursuit of lab research that led me to panic attacks and how I couldn’t understand at the time that it was because my daily efforts were not bringing me joy and instead making me stressed. An easy mistake to make for us all.
I think of my female patients with ADHD or autism who are late-diagnosed or who don’t even have the diagnosis yet who face multiple barriers to self-care including a propensity to mask and override their preferences in this neurotypical world. Even if they did become aware of their masking they still may not be able to read their own body signals to know what is helpful. A recent study suggests that neurodivergent women have a higher risk of rheumatologic diseases, which makes me wonder if this is due to their inability to activate their Nrf-2 effectively.
Bridging Science and Practice
Ultimately, I don’t think Nrf-2 is the answer to all of my patient’s problems, but it is safe to assume the body has self-regulating mechanisms for healing (whether it’s through Nrf-2, bdnf, or a number of other candidates) which some of us may be able to intuitively access better than others. I try to bridge the gap between what my patients’ bodies and feelings may be telling them and the choices they make, much like I needed to bridge that gap for myself. And sometimes that process might require taking it to a cellular level.
So the next time somebody rolls their eyes at the words “self-care,” just quickly interject with “and by self-care I mean activating our Nrf-2 master control transcription factor to regulate oxidative stress in our cells” and see for yourself the response you will get.
