Regenerative Medicine for Chronic Inflammation

Chronic inflammation is increasingly recognised as a central driver of age-related disease, tissue degeneration, and accelerated biological ageing. Unlike the acute inflammation that occurs in response to injury or infection, a beneficial, self-limiting process, chronic inflammation persists at low levels over months and years, progressively damaging tissues and undermining the body’s regenerative capacity. This article examines the biology of chronic inflammation, its relationship to ageing and disease, and how regenerative medicine offers evidence-based approaches to address inflammatory pathways.

Understanding Chronic Inflammation

Inflammation is a fundamental biological response that protects the body from harm. When tissue is injured or infected, the immune system deploys inflammatory mediators, cytokines, chemokines, and immune cells, to neutralise threats, clear debris, and initiate repair.

Acute inflammation follows a well-defined sequence: injury triggers an inflammatory cascade, the threat is contained, and resolution pathways actively return the tissue to homeostasis. This entire process typically resolves within days to weeks.

Chronic inflammation, by contrast, represents a failure of resolution. Instead of returning to baseline, the inflammatory response persists at a low but continuous level, creating a sustained state of immune activation that gradually damages healthy tissue.

The molecular hallmarks of chronic inflammation include:

Persistently elevated levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-α). Increased circulating levels of C-reactive protein (CRP) and other acute-phase reactants. Activation of the NF-κB signalling pathway, a master regulator of inflammatory gene expression. Accumulation of senescent cells that secrete pro-inflammatory molecules (the senescence-associated secretory phenotype, or SASP). Persistent activation of innate immune cells, particularly macrophages, in a pro-inflammatory (M1) phenotype.

Inflammaging: The Inflammation-Ageing Connection

The term “inflammaging” was coined by Italian immunologist Claudio Franceschi to describe the chronic, sterile, low-grade inflammation that accompanies biological ageing. Inflammaging is now considered one of the most significant features of the ageing process and a major contributor to age-related disease.

Several factors drive inflammaging:

Cellular Senescence

As cells accumulate damage throughout life, an increasing number enter a state of senescence, they cease dividing but resist death, instead remaining metabolically active and secreting a complex mixture of pro-inflammatory cytokines, chemokines, proteases, and growth factors known as the SASP. This secretory profile promotes inflammation in surrounding tissues and can induce senescence in neighbouring cells, creating a self-propagating cycle.

Gut Microbiome Dysregulation

The composition and diversity of the gut microbiome change with ageing, often shifting towards a more pro-inflammatory profile. Increased intestinal permeability (sometimes referred to as “leaky gut”) allows bacterial products such as lipopolysaccharide (LPS) to enter the circulation, triggering systemic immune activation and contributing to chronic inflammation.

Immune System Decline

Immunosenescence, the age-related decline in immune function, paradoxically contributes to increased inflammation. As the adaptive immune system becomes less effective, the innate immune system compensates with heightened baseline activity, leading to increased production of inflammatory mediators.

Metabolic Dysfunction

Insulin resistance, visceral adiposity, and metabolic syndrome are associated with elevated inflammatory markers. Adipose tissue is not merely a storage depot but an active endocrine organ that secretes pro-inflammatory adipokines when expanded or dysfunctional.

Accumulated Damage

Years of exposure to environmental toxins, oxidative stress, and metabolic byproducts result in the accumulation of damaged molecules and cellular debris that stimulate inflammatory responses.

Chronic Inflammation and Disease

The downstream consequences of chronic inflammation are extensive. Inflammaging is now implicated in the pathogenesis of:

Cardiovascular disease: Chronic inflammation drives atherosclerosis, promotes plaque instability, and increases the risk of heart attack and stroke. Neurodegenerative diseases: Neuroinflammation contributes to the progression of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions. Type 2 diabetes: Inflammation impairs insulin signalling and contributes to beta-cell dysfunction. Osteoarthritis and joint degeneration: Chronic intra-articular inflammation accelerates cartilage breakdown and joint destruction. Cancer: Chronic inflammation promotes a tissue environment that supports tumour initiation, progression, and metastasis. Sarcopenia: Inflammatory cytokines promote muscle protein breakdown and impair muscle regeneration. Accelerated biological ageing: Inflammation drives multiple hallmarks of ageing, including telomere shortening, epigenetic drift, and mitochondrial dysfunction.

Regenerative Approaches to Chronic Inflammation

Regenerative medicine offers several evidence-based strategies for addressing chronic inflammation at its biological roots:

Mesenchymal Stem Cell Therapy

MSCs are potent immunomodulators. When administered therapeutically, they secrete anti-inflammatory factors including IL-10, TGF-β, and prostaglandin E2 (PGE2) that suppress pro-inflammatory pathways and promote immune tolerance.

MSCs also shift macrophage polarisation from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, fundamentally changing the inflammatory character of the tissue microenvironment. Multiple clinical studies have demonstrated that MSC therapy can reduce systemic inflammatory markers in conditions characterised by chronic inflammation.

Exosome Therapy

MSC-derived exosomes carry anti-inflammatory miRNAs (such as miR-146a and miR-21) that downregulate inflammatory gene expression in recipient cells. As cell-free biological agents, exosomes offer a targeted approach to modulating inflammatory pathways without the complexity of whole-cell administration.

Preclinical evidence shows that exosome therapy can reduce joint inflammation in osteoarthritis models, attenuate neuroinflammation, and modulate systemic inflammatory markers.

Peptide Therapy

Several peptides used in regenerative medicine have demonstrated anti-inflammatory properties:

BPC-157: Modulates inflammatory cytokine production and reduces inflammation in gastrointestinal, musculoskeletal, and neurological models. Thymosin Alpha-1: Promotes immune regulation and reduces excessive inflammatory responses through its immunomodulatory effects on T cells, dendritic cells, and NK cells. Thymosin Beta-4 (TB-500): Has demonstrated anti-inflammatory and tissue-protective effects in multiple preclinical models, supporting the resolution of inflammation and promoting tissue repair.

NAD+ Therapy

NAD+ repletion supports the activity of sirtuins, which play important roles in inflammatory regulation. SIRT1, in particular, deacetylates and inactivates NF-κB, the master inflammatory transcription factor, thereby reducing the expression of pro-inflammatory genes.

By restoring NAD+ levels, NAD+ therapy may help address one of the underlying molecular drivers of inflammaging: the age-related decline in sirtuin-mediated inflammatory control.

PRP Therapy

Platelet-rich plasma contains concentrated anti-inflammatory mediators, including interleukin-1 receptor antagonist (IL-1Ra), that can modulate the inflammatory environment within joints and other target tissues. In osteoarthritis, PRP therapy has been shown to reduce intra-articular inflammation and create conditions more favourable to cartilage preservation and repair.

A Comprehensive Anti-Inflammatory Strategy

Effective management of chronic inflammation requires a multi-faceted approach that addresses the multiple drivers of inflammaging:

Regenerative therapies: MSC, exosome, peptide, and PRP therapies target inflammatory pathways at the molecular and cellular level.

Nutritional optimisation: Anti-inflammatory dietary patterns (rich in omega-3 fatty acids, polyphenols, and fibre; low in processed foods, refined sugars, and industrial seed oils) have been shown to reduce inflammatory biomarkers.

Gut health: Restoring gut barrier integrity and microbiome diversity through targeted nutritional and peptide interventions (including BPC-157) can reduce the translocation of bacterial products that drive systemic inflammation.

Exercise: Regular physical activity has potent anti-inflammatory effects, reducing circulating levels of IL-6, TNF-α, and CRP whilst increasing anti-inflammatory myokines.

Sleep optimisation: Poor sleep is associated with elevated inflammatory markers. Addressing sleep quality and duration is an essential component of any anti-inflammatory programme.

Stress management: Chronic psychological stress activates inflammatory pathways through the hypothalamic-pituitary-adrenal (HPA) axis. Stress reduction techniques can measurably reduce inflammatory burden.

Measuring Inflammatory Status

Comprehensive inflammatory profiling is essential for designing targeted anti-inflammatory interventions. Key measurements include:

High-sensitivity CRP (hs-CRP) as a general inflammatory marker. Pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) for more specific characterisation. Anti-inflammatory cytokines (IL-10, TGF-β) to assess the balance of the inflammatory response. Oxidative stress markers to evaluate free radical damage. Gut permeability markers where intestinal barrier dysfunction is suspected.

At Longevity Thailand, inflammatory profiling is integrated into the comprehensive biomarker assessment that precedes every treatment protocol. This ensures that anti-inflammatory interventions are precisely targeted to each patient’s inflammatory profile.

The Importance of Resolution

A critical concept in modern inflammation biology is that the resolution of inflammation is not simply the absence of pro-inflammatory signals, it is an active, coordinated process mediated by specialised pro-resolving mediators (SPMs), including resolvins, protectins, and maresins derived from omega-3 fatty acids.

Failure of resolution, rather than excessive initiation, may be the primary defect in chronic inflammatory conditions. Regenerative medicine approaches that support resolution pathways, alongside those that suppress initiation, offer a more complete strategy for addressing the inflammatory burden that drives ageing and disease.