Therapeutic Delivery of Ang(1-7) via Genetically Modified Probiotic: A Dosing Study

Area of Science:

• Biogerontology
• Microbiology
• Molecular Biology

Background:

• The renin-angiotensin system (RAS) has emerging roles beyond blood pressure regulation, particularly the ACE2/Angiotensin (1-7)/MAS receptor axis.
• RAS components are present in tissues, with high ACE2 mRNA in the gut, making it a target for therapeutic intervention.
• Genetically engineered probiotics offer precise delivery of therapeutic proteins, with Angiotensin (1-7)-secreting Lactobacillus paracasei (LP-A) previously studied for diabetes and hypertension.

Purpose of the Study:

• To provide proof of concept for using LP-A in a rodent model of aging (Fisher344 x Brown Norway Rat).
• To investigate the potential of LP-A as a novel therapeutic strategy for aging.
• To establish a preclinical model for evaluating LP-A's impact on age-related physiological changes.

Main Methods:

• Administration of Angiotensin (1-7)-secreting Lactobacillus paracasei (LP-A) to aging rats.
• Treatment regimens included 3 or 7 times per week for 4 weeks.
• Measurement of circulating Angiotensin (1-7) levels at acute and chronic time points (8 and 28 days).

Main Results:

• LP-A administration significantly increased circulating Angiotensin (1-7) levels.
• Elevated Angiotensin (1-7) levels were observed both acutely and chronically following treatment.
• The study provides evidence for the efficacy of LP-A in modulating RAS components in an aging model.

Conclusions:

• LP-A effectively increases circulating Angiotensin (1-7) levels in aging rats.
• This probiotic-based approach shows promise for targeting the RAS in the context of aging.
• Future studies will examine the effects of LP-A on gut, brain, and muscle tissues in aging.