Do Infection-Fighting Peptides in Urine Change as We Age? A Study of 308 Adults | Research

The takeaway

Most urinary antimicrobial peptides remain stable with age, but beta-defensin-2 is significantly lower in older adults — a finding that may help explain increased UTI susceptibility in aging populations.

hBD-2 significantly lower in adults 65+
While three other urinary antimicrobial peptides showed no age-related changes, beta-defensin-2 was significantly reduced in older men (p < .001) and women (p = .004), suggesting a specific gap in urinary innate immunity with aging.

What the researchers found

In a study of 308 adults, three of four urinary antimicrobial peptides (HNP 1-3, HD-5, and LL-37) showed no significant differences between adults aged 65+ and those under 65. However, human beta-defensin-2 (hBD-2) was significantly lower in older adults of both sexes (p < .001 for males, p = .004 for females). Additionally, urine leukocyte esterase was associated with increased HNP 1-3 and HD-5 levels, hematuria with increased hBD-2, and contaminated urine cultures with increased HNP 1-3 and hBD-2.

Why it matters

Older adults are much more susceptible to urinary tract infections, and understanding whether their innate immune defense peptides in urine change with age could explain this vulnerability. The finding that hBD-2 specifically declines with age while other antimicrobial peptides remain stable suggests a targeted gap in urinary tract defense that could be investigated as both a diagnostic marker and a potential therapeutic target.

How the study worked

Cross-sectional study of 308 patients aged 18 and older at a family medicine clinic during nonacute visits. Urine samples were analyzed using enzyme-linked immunosorbent assays (ELISA) for four antimicrobial peptides: HNP 1-3, HD-5, hBD-2, and LL-37. Associations between age and AMP levels were tested using both unadjusted and multivariable linear regression models.

Who was studied

308 adults aged 18+ attending nonacute family medicine clinic visits, with 144 (46.8%) aged 65 or older

What this study cannot tell us

The cross-sectional design captures a single time point and cannot track changes in individual patients over time. The study was conducted at a single family medicine clinic, which may limit generalizability. The sample size of 308, while reasonable, may not capture the full range of variability across different age groups, ethnicities, or health conditions.

How to read the evidence

This is a prospective observational cross-sectional study with a well-defined methodology (ELISA measurements, multivariable regression). While it provides strong baseline data, the cross-sectional design limits causal conclusions and the single-site recruitment may affect generalizability.

When this study was published

Published in 2024, this is a recent study establishing baseline reference values for urinary antimicrobial peptides by age — an area with very limited prior data.

The bigger picture

Urinary tract infections are among the most common infections in older adults and a major cause of hospitalization. This study provides foundational baseline data on urinary antimicrobial peptide levels by age, which is essential for any future use of these peptides as diagnostic biomarkers. The selective decline in hBD-2 with aging also points toward a specific innate immunity gap that could eventually be targeted therapeutically.

Questions still open

Could supplementing or boosting beta-defensin-2 levels in older adults reduce their UTI susceptibility?
Can urinary antimicrobial peptide levels reliably distinguish between UTI and asymptomatic bacteriuria in elderly patients?
What biological mechanisms cause the age-related decline in hBD-2 while other antimicrobial peptides remain stable?

Common questions

What are antimicrobial peptides and what do they do in urine?

Antimicrobial peptides (AMPs) are small proteins produced by your body as part of its innate immune defense. In the urinary tract, they act as a first line of defense against bacteria, helping to prevent infections before they take hold. Think of them as natural antibiotics that your body produces on its own.

Why are older adults more prone to urinary tract infections?

Multiple factors contribute, including weakened immune function, hormonal changes, incomplete bladder emptying, and greater use of catheters. This study adds a new piece to the puzzle: older adults have lower levels of beta-defensin-2, a key infection-fighting peptide in urine, which may create a gap in the urinary tract's natural defense system.

Read the original research

Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study.

The journals of gerontology. Series A, Biological sciences and medical sciences, 79(6)

View on PubMed ↗Publisher’s paper ↗

Citation

Caterino, Jeffrey M; Stephens, Julie A; Wexler, Randell; Camargo, Carlos A; Hunold, Katherine M; Wei, Lai; Hains, David; Southerland, Lauren T; Bischof, Jason J; Schwaderer, Andrew. (2024). Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study.. The journals of gerontology. Series A, Biological sciences and medical sciences, 79(6). https://doi.org/10.1093/gerona/glad223