Candidate molecular targets uncovered in mouse lifespan extension studies

ABSTRACT

Introduction

Multiple interventions have demonstrated an increase in mouse lifespan. However, non-standardized controls, sex or strain-specific factors, and insufficient focus on targets, hinder the translation of these findings into clinical applications.

Areas covered

We examined the effects of genetic and drug-based interventions on mice from databases DrugAge, GenAge, the Mouse Phenome Database, and publications from PubMed that led to a lifespan extension of more than 10%, identifying specific molecular targets that were manipulated to achieve the maximum lifespan in mice. Subsequently, we characterized 10 molecular targets influenced by these interventions, with particular attention given to clinical trials and potential indications for each.

Expert opinion

To increase the translational potential of mice life-extension studies to clinical research several factors are crucial: standardization of mice lifespan research approaches, the development of clear criteria for control and experimental groups, the establishment of criteria for potential geroprotectors, and focusing on targets and their clinical application. Pinpointing the targets affected by geroprotectors helps in understanding species-specific differences and identifying potential side effects, ensuring the safety and effectiveness of clinical trials. Additionally, target review facilitates the optimization of treatment protocols and the evaluation of the clinical feasibility of translating research findings into practical therapies for humans.

KEYWORDS:

• Aging
• geroprotectors
• interventions
• lifespan
• longevity
• targets
• therapy

Article highlights

• In vivo, mouse models are extensively utilized to study methods for extending lifespan, but the effectiveness of these strategies in translating to humans varies.

• Standardization of parameters assessed in mouse experiments on lifespan extension is crucial for translating therapies into the clinic.

• To move from mouse studies to clinical applications, it is necessary to conduct a thorough review of the target.

• Through the examination of different interventions has been determined 10 specific targets that have led to a significant increase in the absolute maximum lifespan of experimental animals by at least 10% compared to the control group: mTOR, AMPK, GHRH/IGF1, KLF1, Syntaxin 4, TERT, FGFR1, MIF, BRD2, and FAT10.

• We have thoroughly examined the clinical application, ongoing clinical trials, and potential outlook of these targets.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary materials

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14728222.2024.2346597

Additional information

Funding

This manuscript was funded by the program “Priority 2030”.