Aging Rodent Models

Introduction

Aging rodent models are essential tools in biomedical research, offering insights into the mechanisms of aging and potential interventions to extend lifespan and healthspan. These models, particularly mice and rats, are widely used due to their genetic, physiological, and metabolic similarities to humans. Research in this area focuses on understanding aging processes and developing strategies to mitigate age-related decline.

Key Findings in Rodent Aging Research

Lifespan Extension

Studies have demonstrated that certain interventions can significantly extend the lifespan of rodents. For instance, rapamycin, an immunosuppressant and antibiotic, has shown promise in extending the lifespan of mice by 9%-14% and up to 61% in some cases. Rapamycin works by inhibiting the mechanistic target of rapamycin (mTOR), a key regulator of cellular growth and metabolism.

Healthspan Improvement

Beyond lifespan, research emphasizes improving healthspan—the period of life spent in good health. Interventions like caloric restriction, intermittent fasting, and mTOR inhibition enhance cellular maintenance and repair, reducing the accumulation of damaged proteins and cellular stress. These approaches have been shown to improve overall health and delay the onset of age-related diseases in rodents.

Gene Therapy

Emerging research in gene therapy has also shown potential in aging rodent models. For example, intravenous, high-dose AAV gene therapy to upregulate VEGF has been demonstrated to extend life in mice. This therapy addresses age-related disruptions in angiogenesis, promoting the maintenance of capillary networks and improving tissue health.

Hormesis and Lifespan

The concept of hormesis—a biphasic dose response to stressors—has been explored in rodent models. Research indicates that mild stressors, such as dietary restrictions, phytochemicals, and exercise, can extend lifespan by enhancing biological plasticity and resilience. Studies across various rodent models have shown consistent lifespan extensions of 30-60%, highlighting the potential of hormetic interventions in aging research.

Translational Potential

While aging rodent models provide valuable insights, translating these findings to humans requires careful consideration. The Test of Rapamycin in Aging Dogs (TRIAD) trial investigates rapamycin's effects on dogs, which share many age-related diseases and physiological similarities with humans. However, the translational efficacy of rapamycin in humans remains unclear due to side effects and the complexity of human aging.

Conclusion

Aging rodent models are indispensable in the study of aging and lifespan extension. Interventions such as rapamycin, caloric restriction, gene therapy, and hormetic approaches have shown significant potential in improving both lifespan and healthspan in rodents. While these findings offer promising avenues for research, further studies are needed to understand their applicability and safety in humans. Continued exploration of aging mechanisms and interventions in rodent models will pave the way for advancements in human aging research and public health.