Serotonin

What serotonin does and why it matters for aging

Serotonin is a neurotransmitter that regulates mood, sleep, appetite, pain perception, and social behavior. About 95% of it is produced in the gut by enterochromaffin cells, not in the brain. This fact makes the gut-brain axis central to how serotonin affects your mental and physical health. Brain serotonin and gut serotonin are separate pools: serotonin can't cross the blood-brain barrier, so the brain has to make its own from tryptophan transported across the barrier ^[1].

Here's what gets less attention: serotonin receptor density declines with age. A meta-analysis of 31 PET and SPECT imaging studies found that 5-HT2A receptors decline substantially across the lifespan, with losses of 2-7% per decade depending on the brain region ^[2]. The largest drops happen in the frontal cortex and hippocampus. This decline tracks with age-related changes in sleep quality, mood regulation, and cognitive flexibility. In animal models, dietary restriction preserved serotonin and dopamine levels into late life and slowed the behavioral deterioration that normally comes with aging ^[3].

How serotonin is made: tryptophan, cofactors, and timing

Serotonin synthesis starts with tryptophan, an essential amino acid found in turkey, cheese, nuts, seeds, eggs, and fish. But eating tryptophan-rich foods alone isn't enough. Tryptophan competes with other large neutral amino acids for transport across the blood-brain barrier. Moderate carbohydrate intake triggers insulin release, which clears competing amino acids from the bloodstream and gives tryptophan a transport advantage. This is one reason why very low-carb diets can worsen mood in some people.

The conversion of tryptophan to serotonin requires the enzyme tryptophan hydroxylase plus vitamin B6 and tetrahydrofolate as cofactors. Timing matters too. Bright light exposure, especially morning sunlight, activates tryptophan hydroxylase gene expression. Researchers found that serotonin production rates in the brain directly correlate with the duration of bright sunlight on a given day ^[4]. Exercise also increases tryptophan availability in the brain: one study showed a 30% rise in tryptophan levels across multiple brain regions during running ^[5]. Peak brain serotonin levels occur in late morning, following the circadian pattern set by light exposure.

The gut microbiome connection

Since the gut produces most of the body's serotonin, microbiome health directly affects serotonin status. Specific bacterial species contribute here: Faecalibacterium prausnitzii, Roseburia species, and various Bacteroides strains support tryptophan precursor availability and produce short-chain fatty acids that maintain intestinal barrier integrity. When the gut barrier becomes permeable (sometimes called "leaky gut"), bacterial lipopolysaccharides enter circulation and impair serotonergic signaling ^[1].

A 2024 review found that probiotics can modulate serotonin levels through multiple pathways: stimulating enterochromaffin cell production, modulating the serotonin transporter (SERT), and producing neuroactive metabolites that signal through the vagus nerve ^[6]. Fiber intake above 30 grams per day supports the bacterial taxa most involved in serotonin precursor production. This isn't abstract biology. Population studies consistently link higher fiber intake and greater microbial diversity with lower rates of depression.

Practical ways to support serotonin levels

Serotonin optimization works best when you address multiple inputs at once rather than relying on a single fix.

• Morning light: 10-30 minutes of outdoor light within an hour of waking drives tryptophan hydroxylase expression and anchors your circadian rhythm
• Aerobic exercise: 20-40 minutes of moderate-intensity movement raises brain tryptophan and activates serotonergic pathways. Consistency matters more than intensity.
• Diet: Tryptophan-rich whole foods (legumes, nuts, seeds, eggs, fish) combined with moderate complex carbohydrates. Don't forget B6 and folate from leafy greens and whole grains.
• Fiber: 30+ grams daily from diverse plant sources to feed serotonin-supporting gut bacteria
• Sleep: 7-9 hours of quality sleep supports serotonin synthesis and circadian regulation. Sleep deprivation directly impairs serotonergic function.

Chronic stress, poor sleep, and highly processed diets all work against serotonin production. The payoff of addressing these basics goes well beyond mood: serotonin affects gut motility, bone density, wound healing, and cardiovascular function. If you suspect clinically low serotonin or experience persistent depression, consult a healthcare professional. Lifestyle optimization complements but doesn't replace medical treatment when it's needed ^[7].