How Targeting Inflammaging Could Reverse the Tide of Age-Related Disease
A new narrative review maps the leading therapeutic strategies against inflammaging — from senolytics to NAD+ boosters — and their potential to tackle multimorbidity.
Summary
Inflammaging — the chronic, low-grade inflammation that accumulates with age — is now recognized as a central driver of multimorbidity in older adults. This narrative review surveys the most promising therapeutic approaches to counteract it. Senolytic drugs like dasatinib plus quercetin and fisetin selectively clear senescent cells, reducing the harmful secretory signals they emit. Senomorphic agents such as rapamycin and JAK inhibitors suppress those signals without killing cells. Restoring NAD+ through supplements like nicotinamide riboside and nicotinamide mononucleotide shows early benefits for vascular and metabolic health. Anti-inflammatory biologics targeting IL-1β, IL-6, and TNF-α have already demonstrated cardiovascular benefit. Repurposed drugs — metformin, SGLT2 inhibitors, GLP-1 agonists — add further anti-inflammatory value. Lifestyle interventions including caloric restriction, exercise, and Mediterranean diet remain foundational. Major gaps include lack of validated biomarkers and long-term safety data.
Detailed Summary
As global populations age, the burden of simultaneous chronic conditions — multimorbidity — has become one of medicine's most pressing challenges. A central biological mechanism linking these conditions is inflammaging: a persistent, low-grade inflammatory state now recognized as a hallmark of biological aging. A 2026 narrative review published in Clinical Interventions in Aging synthesizes the current landscape of therapies designed to target this process.
The review focuses on three core mechanisms. First, cellular senescence and the senescence-associated secretory phenotype (SASP): aging cells that refuse to die continue releasing pro-inflammatory cytokines and enzymes that damage surrounding tissue. Senolytic combinations — most notably dasatinib plus quercetin, and the natural flavonoid fisetin — have shown the ability to reduce circulating SASP markers in early-phase human trials. Senomorphic agents, including rapamycin and JAK inhibitors, offer an alternative by blunting SASP output while leaving cells intact.
Second, the review addresses declining NAD+ levels, which impair mitochondrial function and cellular repair. Supplementation with nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) has produced measurable improvements in vascular function and metabolic parameters in early human studies. Inhibiting CD38, an enzyme that consumes NAD+, may complement these approaches by preserving available NAD+ pools.
Third, targeted anti-inflammatory biologics against cytokines such as IL-1β, IL-6, and TNF-α have already translated into clinical benefits — particularly in cardiovascular disease — validating the inflammation-targeting paradigm. Repurposed metabolic drugs including metformin, SGLT2 inhibitors, and GLP-1 receptor agonists also carry meaningful anti-inflammatory properties and are increasingly viewed through a longevity lens.
Evidence-based lifestyle interventions — caloric restriction, regular exercise, and Mediterranean dietary patterns — are emphasized as indispensable complements to pharmacological strategies. The review closes with a candid acknowledgment of obstacles: validated inflammaging biomarkers are scarce, trial designs for multimorbid populations are complex, and long-term safety data for most of these agents remain limited. Combination and precision approaches represent the next frontier.
Key Findings
- Senolytic combos (dasatinib + quercetin, fisetin) reduce circulating SASP factors in early human clinical trials.
- NR and NMN supplementation improves vascular function and metabolic health in early human studies.
- Biologics targeting IL-1β, IL-6, and TNF-α show clinical cardiovascular benefit, validating the inflammaging model.
- Metformin, SGLT2 inhibitors, and GLP-1 agonists exhibit anti-inflammatory effects relevant to aging.
- Exercise, caloric restriction, and Mediterranean diet remain foundational strategies for mitigating inflammaging.
Methodology
This is a narrative review — not a systematic review or meta-analysis — and therefore does not apply formal literature search protocols or risk-of-bias assessments. The author synthesized published research on inflammaging mechanisms and therapeutic strategies, drawing on preclinical studies, early-phase clinical trials, and epidemiological evidence. No original data were generated.
Study Limitations
The summary is based on the abstract only, as the full text was not accessible; detailed data, citations, and nuanced discussion may differ from what is presented here. As a narrative review, the work is subject to selection bias and does not provide pooled effect sizes or formal evidence grading. Long-term safety data for most featured therapies — particularly senolytics in older, multimorbid populations — are still lacking.
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