Longevity LifehacksEvidence Map
Conditions/Inflammaging & immune aging
Condition

Inflammaging & immune aging

Debbie describes inflammaging as low-grade, chronic inflammation that rises with age and underlies many diseases of aging. A central theme is that resolving inflammation is an active process that depends on pro-resolving mediators (SPMs) made from DHA and EPA, and aged tissues make inflammation but not enough resolution. She traces sources of chronic inflammation to senescent cells the immune system fails to clear, and to tissue damage such as digestive enzymes escaping the gut. A 2025 study shifted her view: inflammaging looks largely like a byproduct of industrialized lifestyles, so she now emphasizes preventing its causes while keeping a robust immune response.

How it connects

Resolving inflammation is an active process driven by SPMs made from DHA and EPA, and in animal studies aged muscle made plenty of inflammatory signals but too few pro-resolving mediators.

Stopping Inflammaging: SPMs to the Rescue

Non-industrialized populations (Tsimane, Orang Asli) showed little age-related rise in inflammatory markers, suggesting inflammaging is shaped by modern lifestyle rather than inevitable.

Rethinking a Hallmark of Aging: Inflammaging

In mice, chronic PGE2 signaling through the EP2 receptor stops macrophages from clearing senescent neutrophils, and PGE2 is made from omega-6 arachidonic acid.

Aging, Inflammation, and the Failure to Clear Senescent Cells

In aged rats, digestive enzymes leaking through a thinned gut mucosal barrier damaged organs, suggesting a systemic source of the tissue damage that drives inflammaging.

A New Theory of Why We Break Down in Old Age

Modern exposures like sucralose, microplastics, pesticides, and food additives change the gut microbiome, which is central to balancing immune responses throughout the body.

Rethinking a Hallmark of Aging: Inflammaging

Mitochondrial decline makes immune cells prone to 'exhaustion,' which links energy metabolism to infections and inflammaging.

Mitochondrial Function and Age-Related Inflammation: Urolithin A

Interventions, strongest evidence first

Vitamin D3 (incl. HMB + vitamin D) Sunlight-made hormone that regulates immunity and muscle; linked to slower telomere shortening and preserved function in trials. Supplement Muscle, skinInflammagingAlzheimer's 8 posts
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Ketones (exogenous ketones & MCT) Alternative fuel that lets the energy-starved failing heart pump better; BHB also dampens NLRP3 inflammation. Supplement HeartAlzheimer'sInflammaging 4 posts
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Omega-3s (DHA/EPA) & SPMs DHA and EPA are the building blocks for pro-resolving mediators that actively switch off inflammation. Supplement InflammagingAlzheimer'sHeartMuscle, skin 14 posts
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Glycine Amino acid that supports glutathione production with NAC and may deepen slow-wave sleep. Amino acid Alzheimer'sInflammagingHeartMuscle, skin 4 posts
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N-acetylcysteine (NAC) Cysteine source that cells use to make glutathione, the antioxidant that declines with age. Amino acid Alzheimer'sInflammagingHeartMuscle, skin 7 posts
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NAD+ precursors (NR, NMN) and CD38 inhibition NR and NMN feed the NAD+ salvage pathway to offset the age-related NAD+ decline driven partly by CD38. Supplement Alzheimer'sHeartInflammagingMuscle, skin 12 posts
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Taurine Sulfur-containing amino acid whose levels decline with age; supplementation extended median lifespan in mice. Amino acid HeartMuscle, skinInflammaging 5 posts
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C15:0 (Pentadecanoic Acid) Odd-chain saturated fat linked to better metabolic and heart health in observational studies; supplement trials show minimal effect. Supplement HeartGut barrierInflammaging 1 posts
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Arginine Semi-essential amino acid that fuels T cells and feeds spermidine; reduced amyloid-beta in Alzheimer's mice. Amino acid Alzheimer'sInflammagingGut barrierHeart 6 posts
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L-Glutamine Abundant amino acid fueling gut lining cells and mucus; she takes it to protect the gut barrier. Amino acid Gut barrierInflammagingHeart 5 posts
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Light at Night & Melatonin Bright days and dark nights maximize melatonin, an antioxidant linked to lower mortality and Alzheimer's protection. Diet & lifestyle Alzheimer'sHeartInflammagingGut barrier 11 posts
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Curcumin Turmeric polyphenol that lowers TNF-alpha and other inflammatory signals; she takes it to curb NLRP3 overactivation. Supplement InflammagingAlzheimer'sHeartMuscle, skin 12 posts
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Resveratrol Grape polyphenol in her stack, linked to heart health, lower inflammation, FOXO3/sirtuin activation, and fading age spots. Supplement HeartAlzheimer'sInflammagingMuscle, skin 13 posts
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Proline Collagen-rich amino acid that restored mitochondrial function in senescent stem cells in a 2024 study. Amino acid Muscle, skinInflammaging 3 posts
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Spermidine Polyamine that induces autophagy and declines with age; extends lifespan in model organisms. Supplement Alzheimer'sHeartInflammagingMuscle, skin 2 posts
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Fisetin & Quercetin Plant flavonoids studied as senolytics that clear senescent 'zombie' cells and dampen inflammatory signaling. Supplement InflammagingHeartAlzheimer'sMuscle, skin 12 posts
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Alpha-Ketoglutarate (AKG) Krebs-cycle metabolite that drops sharply with age; supplementation extended lifespan and healthspan in mice. Supplement InflammagingHeartMuscle, skin 4 posts
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Lithium (low-dose lithium orotate) Trace mineral found in food and water; low brain lithium is linked to Alzheimer's amyloid, tau, and neuroinflammation. Supplement Alzheimer'sInflammagingHeart 8 posts
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GHK-Cu (copper peptide) Copper-binding tripeptide that declines with age and supports skin, wound healing, hair and lung repair. Peptide Muscle, skinInflammaging 1 posts
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Urolithin A Gut-microbe metabolite of ellagitannins that boosts mitophagy and may counter age-related immune decline. Supplement InflammagingGut barrier 3 posts
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Microplastics Reduction Cutting nanoplastic exposure, found in arterial plaque and brain tissue, and keeping the gut barrier strong. Environment HeartAlzheimer'sGut barrierInflammaging 6 posts
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Luteolin Flavonoid from herbs and vegetables with anti-inflammatory, antihistamine, and possibly neuroprotective effects, mostly shown in cells and animals. Supplement Alzheimer'sInflammaging 6 posts
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Everyday steps