Immune System

Your immune system ages, too

Most people think of the immune system as something that either works or doesn't. The reality is more nuanced. After about age 20, the thymus gland (where T cells mature) begins to shrink. By 50, it's largely replaced by fatty tissue, and the supply of new, naive T cells drops sharply ^[1]. This process, called immunosenescence, explains why older adults respond more poorly to vaccines, catch infections more easily, and develop cancer at higher rates.

At the same time, aging brings a rise in baseline inflammation. Researchers call this "inflammaging": a chronic, low-grade inflammatory state driven by senescent cells, accumulated cellular damage, and shifts in immune cell populations ^[2]. Your body is simultaneously less capable of fighting new threats and more prone to damaging itself through misdirected inflammatory signaling. Understanding this trade-off is the starting point for any serious longevity strategy.

How the immune system actually works

Two branches handle defense. The innate immune system responds within minutes to hours. It includes physical barriers (skin, mucous membranes), chemical defenses (stomach acid, antimicrobial peptides), and cellular responders like macrophages, neutrophils, and natural killer (NK) cells. These cells recognize broad pathogenic patterns and don't need prior exposure to act.

The adaptive immune system takes days to mount a first response but remembers. B cells produce antibodies targeting specific pathogens. Cytotoxic T cells destroy infected or abnormal cells. Helper T cells coordinate the overall response. After an initial encounter, memory cells persist for years or decades, enabling faster reactions on re-exposure. This memory is what makes vaccination work.

The gut connection

Around 70 to 80% of your immune cells reside in gut-associated lymphoid tissue ^[3]. The intestinal microbiome directly trains and calibrates immune responses. Diverse gut bacteria produce short-chain fatty acids (SCFAs) like butyrate, which support regulatory T cells and help maintain immune tolerance. When gut diversity drops or the intestinal barrier weakens, bacterial endotoxins can enter the bloodstream and trigger systemic immune activation. This is one reason gut health and immune health are so tightly linked.

What actually strengthens immune function

Forget "immune boosting" supplements. The immune system is a balance, not a dial you turn up. An overactive immune system causes autoimmune disease and allergies. What you actually want is a well-regulated, responsive immune system. Here's what the evidence supports:

• Sleep: During sleep, your body produces cytokines needed for immune defense and antibody formation. Studies consistently show that sleeping less than 6 hours per night increases susceptibility to respiratory infections by 4.2 times compared to 7+ hours ^[4].
• Exercise: Moderate regular exercise enhances NK cell activity and improves immune surveillance. People who exercise regularly get sick less often, and vaccines work better for them. Aim for 150+ minutes of moderate activity per week ^[5].
• Nutrition: Vitamin D regulates the expression of hundreds of immune-related genes and deficiency is common, especially in northern latitudes. Zinc is a cofactor for over 2,000 human proteins including many in immune signaling. Vitamin C supports neutrophil function. But supplements only help when you're actually deficient ^[6]. A varied diet with sufficient protein, colorful vegetables, and fermented foods covers most people's needs.
• Stress management: Chronically elevated cortisol suppresses lymphocyte proliferation and reduces antibody production. Regular stress reduction through meditation, time outdoors, or social connection measurably improves immune parameters.

Emerging interventions in immune aging

Longevity research is increasingly focused on reversing immunosenescence. Rapamycin (an mTOR inhibitor) has shown promise in improving vaccine responses in older adults ^[7]. Senolytic compounds that clear senescent cells may reduce the inflammatory burden that drives inflammaging. Thymus regeneration research, while still early, aims to restore the organ's ability to produce new T cells. Metformin and NAD+ precursors are also being studied for their immune-modulating effects ^[2].

None of these are ready for routine use yet. For now, the lifestyle fundamentals (sleep, exercise, nutrition, stress management, gut health) remain the most effective and evidence-backed tools for maintaining immune function as you age.