In 2000, Italian immunologist Claudio Franceschi introduced the term "inflammaging" to describe a phenomenon that had been quietly observed in aging research for decades: as we get older, the immune system enters a state of chronic, low-grade activation that never fully resolves. Unlike the acute inflammation that follows an injury or infection — which serves a clear purpose and subsides once the threat is neutralized — inflammaging is a slow, persistent smolder that damages tissues over years and decades.

What Causes Inflammaging?

The origins of inflammaging are multifactorial, and understanding them requires looking at several converging biological processes. A comprehensive 2018 review published in Nature Reviews Cardiology by Ferrucci and Fabbri identified the primary drivers as genetic susceptibility, cellular senescence, immune system dysregulation, gut microbiome disruption, and the accumulation of molecular damage that the body's repair systems can no longer fully clear.[1]

Cellular senescence plays a particularly important role. As cells age and accumulate DNA damage, some enter a state called senescence — they stop dividing but do not die. Instead, they secrete a cocktail of inflammatory cytokines, proteases, and growth factors known as the senescence-associated secretory phenotype (SASP). In small amounts, SASP signals help coordinate tissue repair. But as senescent cells accumulate with age, their collective inflammatory output becomes a chronic burden on surrounding tissue.

The gut microbiome is another significant contributor. Aging is associated with reduced microbial diversity and increased intestinal permeability — a condition sometimes called "leaky gut" — which allows bacterial fragments to enter the bloodstream and trigger systemic immune activation. Research has consistently shown that individuals with more diverse gut microbiomes exhibit lower markers of systemic inflammation and slower biological aging.

The Disease Burden of Inflammaging

The clinical consequences of chronic low-grade inflammation are substantial. Ferrucci and Fabbri's review found that elevated inflammatory markers — particularly interleukin-6 (IL-6) and C-reactive protein (CRP) — are among the strongest predictors of cardiovascular disease, type 2 diabetes, cognitive decline, sarcopenia (muscle loss), and all-cause mortality in older adults.[1] Inflammaging does not cause these conditions directly; rather, it creates the biological environment in which they are far more likely to develop and progress.

For the brain specifically, neuroinflammation driven by inflammaging is now considered a central mechanism in Alzheimer's disease and other dementias. Activated microglia — the brain's resident immune cells — release inflammatory mediators that damage neurons and disrupt synaptic function. This is why many researchers now view Alzheimer's not purely as a protein aggregation disease, but as an inflammatory disease of the aging brain.

NAD+ as an Anti-Inflammaging Intervention

One of the most promising molecular targets for modulating inflammaging is NAD+ — the coenzyme whose decline with age is itself a driver of inflammatory signaling. A 2024 review published in Pharmaceuticals highlighted the essential role of NAD+ in immune regulation, noting that increasing NAD+ levels may reduce inflammatory responses by modulating the CD38 and CD73 pathways — enzymes that consume NAD+ during immune activation.[2] When NAD+ is depleted, these pathways become dysregulated, amplifying the inflammatory cascade.

Sirtuins — the NAD+-dependent proteins that regulate cellular stress responses — also play a direct anti-inflammatory role. SIRT1 and SIRT3, in particular, suppress the activity of NF-κB, the master transcription factor that drives the production of pro-inflammatory cytokines. Restoring NAD+ levels through IV infusion or precursor supplementation effectively reactivates these protective pathways.

Peptides and Targeted Anti-Inflammatory Support

Beyond NAD+, several peptides have demonstrated meaningful anti-inflammatory activity in clinical and preclinical research. A 2018 review in the International Journal of Molecular Sciences documented the potential of therapeutic peptides as anti-inflammatory agents, noting their "high specificity and diverse biological activities" and their ability to modulate inflammatory responses by inhibiting specific inflammatory mediators — with fewer systemic side effects than traditional pharmaceutical approaches.[3]

BPC-157, for example, has been shown to modulate the nitric oxide system and suppress inflammatory signaling in multiple tissue types. GHK-Cu (copper peptide) has demonstrated the ability to downregulate inflammatory gene expression while simultaneously promoting tissue repair. These mechanisms make peptides a compelling complement to nutrient-based anti-inflammatory strategies.

Dietary and Lifestyle Modulation

The research on diet and inflammaging is among the most consistent in the field. A 2021 systematic review published in Nutrients examined the relationship between dietary patterns and chronic inflammation, finding that diets rich in fiber, polyphenols, and omega-3 fatty acids — exemplified by the Mediterranean diet — are consistently associated with lower levels of inflammatory markers and a more favorable gut microbiome composition.[4] The mechanism involves the production of short-chain fatty acids by beneficial gut bacteria, which directly inhibit inflammatory signaling pathways.

Exercise, sleep quality, and stress management are equally important. Chronic psychological stress activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, both of which drive inflammatory cytokine production. Addressing inflammaging comprehensively requires attending to all of these inputs — not just supplementation.

The Clinical Approach at Nectar Wellness

At Nectar Wellness, our approach to longevity and healthy aging is grounded in the science of inflammaging. Our IV therapy blends — including high-dose vitamin C, glutathione, and NAD+ — are formulated to address the oxidative and inflammatory burden that accumulates with age. Our peptide offerings, including BPC-157 and GHK-Cu, provide targeted support for tissue repair and inflammatory modulation. And our nurse-led consultations are designed to help you understand your individual risk factors and build a personalized plan.

"Inflammaging is a significant risk factor for morbidity, disability, and premature death in older persons." — Ferrucci & Fabbri, Nature Reviews Cardiology, 2018