The goal of this clinical trial is to learn if AppleX™ Apple Extract can help lower systemic inflammation in adults aged 45-70 with signs of low-grade inflammation. It will also look at the extract's effects on fatigue, joint comfort, and biological aging metrics.

The main questions it aims to answer are:

• Does taking AppleX™ Apple Extract daily lower high-sensitivity C-reactive protein (hsCRP) levels, a key marker of inflammation in the blood?
• Does AppleX™ Apple Extract improve participant-reported fatigue and joint comfort?
• Does the extract slow down biological or epigenetic aging metrics compared to a placebo?

Researchers will compare AppleX™ Apple Extract to a placebo (a look-alike capsule that contains no active ingredients) to see if the apple extract has a measurable anti-inflammatory and healthy aging effect.

AppleX™ is a whole-apple extract standardized to 15% fisetin, delivering 15 mg of active fisetin within a natural polyphenol matrix of quercetin, chlorogenic acid, and procyanidins. This trial evaluates the physiological effects of continuous, lower-dose daily intake (100 mg/day) over a 24-week period, specifically targeting an aging population sample with mild systemic inflammatory burden.

The study utilizes a fully decentralized clinical trial framework. Biological metrics are collected remotely utilizing home-based, finger-prick dried blood spot (DBS) micro-sampling methodologies to minimize participant burden.

In addition to evaluating systemic inflammation through longitudinal tracking of high-sensitivity C-Reactive Protein (hsCRP), the protocol investigates cellular aging by assessing DNA methylation data. This exploratory analysis utilizes the TruAge testing platform (TruDiagnostic) to evaluate advanced biological clocks, including the DunedinPACE pace-of-aging algorithm and targeted organ-system sub-clocks focused specifically on immune and inflammatory aging profiles.

Inclusion Criteria:

• Age 45-70 years at time of enrollment
• Meets questionnaire-based inflammatory enrichment criteria (at least 2 of 5 risk factors, per Section 4.2)
• Non-smoker (no tobacco or nicotine use within 6 months of enrollment)
• Willing and able to maintain stable diet, exercise habits, and supplement use throughout the 24-week study period
• No major medication changes planned during the study period
• Willing to perform home-based DBS collections at T0, T12, and T24
• Access to a smartphone or computer to complete eConsent and online questionnaires
• Able to provide informed consent via the Alethios eConsent platform

Exclusion Criteria:

• Current use of prescription anti-inflammatory medications including NSAIDs (regular use ≥3x/week), corticosteroids, or DMARDs
• Diagnosis of an autoimmune or inflammatory disease (e.g., rheumatoid arthritis, lupus, IBD, multiple sclerosis)
• Active or unstable cardiovascular disease requiring medication changes during the study period
• History of cancer within the past 5 years (except non-melanoma skin cancer)
• Regular use of supplemental fisetin, quercetin, or resveratrol within 30 days of enrollment
• Pregnancy, breastfeeding, or planning to become pregnant during the study
• Known allergy to apple or apple-derived products
• Body mass index (BMI) >40 kg/m²