Mitigating Mitochondrial RNA Release During Aging to Control Inflammation and Senescence

NCT07596615 | Not Yet Recruiting

• 2 other identifiers: MIRACLEFIS-2024-00858
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The MIRACLE study aims to investigate age-related mitochondrial dysfunction, mitochondrial RNA (mtRNA) release, inflammation, and cellular senescence in adult participants across three age groups. Skin-derived fibroblasts and peripheral blood mononuclear cells (PBMCs) will be isolated from skin biopsy and blood samples to characterize age-related cellular and molecular changes and to test experimental therapeutic strategies identified in preclinical studies. Serum, plasma, and whole-blood RNA will be used for protocol-defined analyses of circulating inflammatory mediators and systemic transcriptional signatures related to inflammation, type I interferon activation, mitochondrial stress response, immune aging, and senescence-associated pathways.

Conditions

Aging; Inflammation; Healthy Ageing

Keywords

mitochondrial dysfunction; skin-derived fibroblasts; mtRNA; PBMCs; senescence; inflammaging

Outcome Measures

Primary Outcomes (5)

• Age-dependent differences in cytosolic release of mitochondrial RNA (mtRNA) in primary human fibroblasts

  Assessment of release of mtRNA in the cytosol of primary fibroblasts isolated from study participants across age groups. Cytosolic mtRNA levels assessed through analysis of the mean fluorescence intensity (MFI) per cell by immunofluorescence.

  Day 1 (at enrollment)

• Age-dependent differences in mitochondrial function in primary human fibroblasts

  Characterization of mitochondrial function parameters in primary fibroblasts isolated from study participants across age groups. Mitochondrial function assessed through analysis of mitochondrial Complex I activity in nmol/min/mg protein by functional ELISA.

  Day 1 (at enrollment)

• Activation of inflammatory pathways in primary human fibroblasts

  Assessment of inflammatory pathway activation markers in fibroblasts isolated from participants across age groups. Inflammatory pathway activation assessed through Interleukin-6 concentration in skin-derived fibroblast culture supernatant in pg/mL

  Day 1 (at enrollment)

• Activation of senescence pathways in primary human fibroblasts

  Assessment of cellular senescence markers and senescence-associated pathway activation in fibroblasts isolated from participants across age groups. Senescence pathway activation assessed as percentage (%) of Senescence-associated β-galactosidase (SA-β-gal)-positive cells per microscopic field.

  Day 1 (at enrollment)

• Comparison of fibroblast findings with PBMC-derived parameters from the same participants

  Integration and comparison of fibroblast-derived molecular data with corresponding PBMC-derived measurements obtained from the same participants as described above.

  Day 1 (at enrollment)

Study Arms (3)

Young adults

EXPERIMENTAL

Female and male volunteers aged 18-40 years

Procedure: Skin biopsy and venous blood sampling

Middle-aged adults

EXPERIMENTAL

Female and male volunteers aged 40-60 years

Procedure: Skin biopsy and venous blood sampling

Elderly adults

EXPERIMENTAL

Female and male volunteers aged 60-90 years

Procedure: Skin biopsy and venous blood sampling

Interventions

Skin biopsy and venous blood sampling PROCEDURE

A single 3-4 mm punch biopsy of forearm skin is performed under local anesthesia (lidocaine 1% with epinephrine 1:100,000) for primary dermal fibroblast isolation. Venous blood is collected by standard phlebotomy from the antecubital fossa (43 mL total volume per participant): 5 mL in SST tube for serum separation, 3 mL in EDTA tube for plasma separation, 32 mL in EDTA tubes for PBMC isolation by density gradient centrifugation, and 3 mL in Tempus Blood RNA tube for whole-blood RNA stabilization. All procedures are performed at a single visit at enrollment. Samples are processed for biospecimen-based ex vivo molecular and cellular analyses; no investigational product is administered to participants.

Elderly adults; Middle-aged adults; Young adults

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female
• Age between 18 and 90 years (stratified in three groups: young, middle-aged, elderly)
• Written informed consent

You may not qualify if:

• Inability to understand the potential risk and benefits of the study
• Legal incapacity
• Subjects who have taken antibiotics, anti-inflammatory drugs, or antihistamines within the past 7 days
• Diagnosis of diabetes mellitus
• Use of anticoagulant medications
• Any subject with a contraindication to the mini-invasive biopsy procedure

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (2)

Laboratory for Targeted Therapy in Autoimmune Diseases

Bergamo, BG, 24126, Italy

Location

Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"

Ranica, BG, 24020, Italy

Location

Related Publications (4)

• Zuber TJ. Punch biopsy of the skin. Am Fam Physician. 2002 Mar 15;65(6):1155-8, 1161-2, 1164.

  PMID: 11925094 BACKGROUND

• Nischal U, Nischal Kc, Khopkar U. Techniques of skin biopsy and practical considerations. J Cutan Aesthet Surg. 2008 Jul;1(2):107-11. doi: 10.4103/0974-2077.44174.

  PMID: 20300359 BACKGROUND

• Yasui Y, Kato H, Oda T, Nakamura M, Morita A. Complications and risk factors of punch biopsy: A retrospective large-scale study. J Dermatol. 2023 Jan;50(1):98-101. doi: 10.1111/1346-8138.16585. Epub 2022 Sep 24.

  PMID: 36151785 BACKGROUND

• Akiyama Y, Norimatsu Y, Ohno Y. Prophylactic antimicrobials may not be needed to prevent surgical site infection after skin biopsy: a retrospective study. Antimicrob Resist Infect Control. 2022 Feb 16;11(1):35. doi: 10.1186/s13756-022-01077-z.

  PMID: 35172906 BACKGROUND

MeSH Terms

Conditions

Inflammation; Mitochondrial Diseases

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Giuseppe Remuzzi

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Central Study Contacts

Luca Perico, PhD

CONTACT

+3903542131; luca.perico@marionegri.it

Miriam Rigoldi, MD

CONTACT

+390354535327; miriam.rigoldi@marionegri.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort, cross-sectional

Study Record Dates

• First Submitted: April 29, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)