The objective is to achieve a thorough understanding of the molecular mechanisms of ageing, particularly how “anti-aging” drugs interact with ageing processes and acute positive and negative perturbations, such as exercise and inactivity. By combining in vivo human/animal models with stable isotope and OMIC analyses, we will gain a comprehensive view of the effects of various drugs (e.g., Rapamune, dasatinib/quercetin, and NAD+ donors) in combating cellular decline in both “natural” ageing and accelerated-ageing models. Additionally, we will investigate how these drugs influence physiological stressors that accelerate ageing, such as high fat or processed diets and immobilization, and how they interact with the positive effects of exercise.

Few studies explore translational human anti-ageing interventions. Our unique expertise in both pre-clinical (at Ritsumeikan) and clinical and metabolic science (at Nottingham), combined with an active clinical trial, positions us ahead of the competition. This agility allows us to seamlessly transition between animal and human studies, addressing what is arguably bioscience’s greatest pursuit: the mitigation of global cellular ageing phenomena beyond the current focus on “disease specificity.”

Sarcopenia, despite medical recognition, lacks effective treatments. Our collaboration aims to pioneer solutions for muscle health that are also relevant to broader trans-organ ageing processes. This partnership crucially also offers graduate students and young researchers from both universities the opportunity to engage with advanced translational research techniques, enriching their academic growth and strengthening the future of this vital field. Through pre-clinical and clinical research, we aim to publish impactful findings and translate them into practical applications.

Over the next few years, studies will focus on “anti-ageing” drug interactions in humans and animal models. Tractable animal models offer novel opportunities. Exercise: Electrical stimulation will be used in aged rats or mice to mimic resistance exercise, while treadmill exercises will simulate aerobic exercise. Physical Inactivity: Casting will be employed to immobilize specific muscle groups, and hindlimb suspension will induce muscle atrophy. Ageing models: Mice will undergo natural ageing or be subjected to premature ageing models, such as mutations or deletions in the Ercc1 gene. Metabolic/molecular Analysis: After interventions, muscles and key organs will be analyzed. Mass spectrometry (led by Dr Atherton) will be used for both OMICs and tracer analyses.

This work will contribute to the next-generation university and society in the following ways:

– Provide new frameworks and diverse models (human/animal) for the study of ageing biology.
– Use novel/nascent stable isotope tracing techniques that can be leveraged by future researchers.
– Generate important new questions and avenues for exploration in ageing biology.
– Train a Japanese researcher in state-of-the-art musculoskeletal and wider cellular biology using both human and animal models.

Ageing and its consequences are arguably the greatest challenges in bioscience, and this research aims to move beyond a focus on disease specificity.

Partnerships:

This research holds significant impact and appeal for researchers across the spectrum of basic and translational science. Its discoveries and applications, including drugs and nutritional interventions, are likely to attract interest from researchers in the pharmaceutical and nutritional sectors. I anticipate that this will lead to the formation of new partnerships and strengthen existing ones. This will be facilitated by increasing the visibility of this research through both published outputs and this profile page at Ritsumeikan. Additionally, it is essential that this research creates opportunities for grant funding from Japanese sources, which I believe my lab’s expertise will help to secure.

Research collaborations:

My core values are as follows:

– Collaborations should be mutual and benefit all partners involved.
– Ensure that all parties achieve optimal outcomes from the research.
– Respect cultural differences in all aspects of collaboration.
– Maintain regular dialogue with collaborators, both in person and online.
– Uphold research integrity as a top priority.
– Provide the best training opportunities for early career researchers.
– View collaborations as a foundation for larger successes that benefit society.