Oxford team to study dietary interventions for improving cardiac health and extending lifespan with Longevity Science Foundation’s support.
The Longevity Science Foundation (LSF) has announced the award of a substantial grant to researchers at the University of Oxford’s Department of Physiology, Anatomy and Genetics for a pioneering study on heart aging. Led by Professor Pawel Swietach, and co-supervised by Dr Richard Siow, the research project entitled Metabolic Mechanisms of Ageing in the Heart – Novel Dietary Interventions for Enhancing Healthspan aims to explore how diet can influence metabolic processes within the heart and potentially delay age-related deterioration. The LSF’s financial support, spread across a three-year period, will cover critical aspects of the study, advancing the understanding of cardiac aging and contributing to future therapies.
The project, beginning in 2024, will focus on the chemical changes to molecules that regulate the heart’s function – specifically studying methylation, a process influenced by diet, which affects metabolic pathways involved in heart aging. As the heart has a limited capacity to regenerate, damage and dysfunction accumulate over time, leading to diseases that contribute to about one-third of deaths globally. The research aims to test whether dietary modifications can reverse or prevent these metabolic changes, with the ultimate goal of discovering potential interventions that enhance cardiac health.
Longevity.Technology: The Longevity Science Foundation’s support of the Oxford study marks a significant step in the organization’s broader effort to tackle age-related diseases; by targeting metabolic mechanisms at the root of heart dysfunction, the LSF is helping to push the boundaries of aging research. The Foundation’s ability to channel critical funding to projects that are often constrained by a lack of resources is vital for scientific advancement, and by providing capital to teams like those at Oxford – who are engaged in potentially transformative research – the LSF is making strides toward its goal of increasing healthspan; that is, not just extending life, but extending the years spent in good health. In a world where the population of adults over 60 is rapidly expanding, efforts like these are increasingly crucial for developing strategies to prevent chronic diseases linked to aging.
Professor Swietach’s team is using genetically altered models to study the effects of elevated methionine, an amino acid whose high levels have been linked to accelerated heart dysfunction in aging. The team seeks to determine whether restricting methionine intake or modifying the diet can slow or reverse these effects. By examining how diet interacts with methylation patterns and heart function, the researchers hope to identify new therapeutic strategies that could extend healthspan by preserving cardiac function in older individuals.
This grant award is a critical boost to the project’s overall budget, enabling the team to pursue more comprehensive research into heart aging and its metabolic drivers. By focusing on methylation processes, the researchers are tapping into an area that has shown increasing relevance in understanding aging mechanisms. The hope is that dietary interventions could become a non-invasive, accessible way to mitigate the effects of heart aging – potentially reducing the burden of heart disease and extending the period of life spent in good health.
SAMe old, SAMe old
Professor Swietach told Longevity.Technology that part of the research will focus on a reactive metabolite called SAMe, which is what methionine is converted into as part of an intercellular reaction. SAMe is a so-called methylating agent that brings about myriad changes ranging from protein modifications to DNA epigenetic changes.
“The level of SAMe is set by (i) the dietary supply of methionine and (ii) the rate at which SAMe is processed further downstream,” explained Swietach. “Intuitively, it would seem sensible to control SAMe levels through dietary restriction of methionine but this is not always feasible or proven to be beneficial. An alternative strategy is to target the downstream processing of SAMe because this offers new treatment opportunities.”
Swietach explained that methionine metabolism involves an intermediate called propionyl-CoA, which is significant because this is shared with number of other amino acids, most notably the branched chain amino acids valine and isoleucine.
“A more complete understanding of pathways is needed to propose and test a refined dietary management strategy that controls methylation better,” he said. “The best dietary intervention may involve combinations of amino acids, or measures that influence their enzymic processing – the long-term objective of our project. We think there is considerable potential in understanding how branched chain amino acids and methionine interact, and this is where we can make impact.”
The human heart has a limited ability to repair and regenerate, making accumulated damage over a lifetime critical for survival. One source of this damage stems from biochemical modifications driven by metabolic changes.
“We often base our understanding of these processes by studying cultured cells or animal models that are supplied with carefully formulated media / diets,” explained Swietach. “Whilst this controls for variability, it may mask issues associated with modern-day diets. We think that pushing metabolism towards one extreme can reveal novel mechanistic insights, and one way of doing so is by studying models with metabolic perturbations that resemble aspects of ageing.”
Swietach explained that by studying the effect of modified diets, the research team aims to find interventions to rescue age-related metabolic dysfunction, not only in the heart but all tissues, including brain, liver or skeletal muscle.
“This could potentially provide therapeutic strategies for neurodegenerative and metabolic conditions leading to dementia, diabetes and frailty, and which could ultimately delay the onset of diseases, reduce their severity, extend healthspan and promote longevity.”
Making a difference
“We eagerly anticipate the outcomes of the research Pawel Swietach’s team will make to the scientific field,” said Joshua C Herring, President & CEO of the LSF.
“We are proud to have the Department of Physiology, Anatomy, and Genetics at the University of Oxford as partners, and we look forward to the mutual impact we will create. As the Foundation seeks and sources substantial additional capital through donations, we plan to continue reverberating through the community via our granting to the best research teams available.”
Professor Swietach expressed his gratitude for the LSF’s support, noting: “We are excited that we can implement an element of longevity research into our portfolio, thanks to support from the LSF. The research we plan is ambitious, innovative, and important, but expensive to run. Every contribution to this effort makes a massive difference to us, and we hope it brings tangible benefits to the wider community.”
The study’s co-supervisor, Dr Richard Siow, echoed these sentiments, highlighting the potential impact of the research: “This research will contribute to a better understanding of metabolic changes in the heart during aging and the mechanisms by which dietary interventions can prevent heart disease.
“We are grateful to the Longevity Science Foundation for enabling this research at the University of Oxford and look forward to contributing to the development of novel interventions to enhance healthy longevity.”
In addition to advancing scientific knowledge, the LSF’s grant will provide essential training opportunities for students and early-career researchers, fostering the next generation of scientists in the field of longevity and aging research. This commitment to cultivating new talent is aligned with the LSF’s broader mission of supporting not only cutting-edge research but also the human capital required to sustain long-term progress in the field of longevity science.
