Human Cardiac Age-OME. A multi-facet approach to understanding healthy ageing of the heart

Guglielmi, Giovanni ORCID: 0000-0002-0509-9666 (2025). Human Cardiac Age-OME. A multi-facet approach to understanding healthy ageing of the heart. University of Birmingham. Ph.D.

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Abstract

The world’s population is ageing, expecting individuals over 65 to represent 38% of the total population by 2050705. As lifestyle and medical practices have improved and one’s life expectancy is longer, comorbidities associated with ageing are also expected to raise healthcare costs in the near future. This can limit access to appropriate medical treatments and introduce further disparities in healthcare accessibility due to one’s socio-economic background556. Older age is a strong risk factor for cardiac morbidity and cardiovascular diseases, including heart failure, one of the leading causes of death. Furthermore, those who survive cardiomyopathies can often be left with disabilities, which would exert financial and
socioeconomic impacts on themselves, family members and the community. The increase in cardiovascular diseases partially attributed to ageing has set a novel and challenging goal for the scientific community: understanding how cardiac tissues age. Although aged hearts might not develop cardiomyopathies, their functionality, shape, histology and molecular composition decrease over time. Frailty of the cardiac muscle is developed around the age of 50, where mortality for cardiovascular diseases arises for both genders. On the other hand, mortality due to non-congenital cardiovascular diseases is almost negligible for young individuals, usually aged between 12 and 25. Utilising a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we analysed the molecular landscape (transcripts, proteins, metabolites and lipids) in young (≤ 25 years old) and old (≥ 50 years old) donors to characterise human cardiac ageing. Analysing all the molecules using multiple biostatistical and mathematical methods, including a novel framework for analysing biological networks and a newly engineered method for detecting dysregulated biological processes, we observed a downregulation of proteins involved in calcium signalling, such as SERCA, decreased abundance in key proteins of the contractile apparatus, like myosin heavy chain, in older hearts. In addition, we found a potential counteractive upregulation of central carbon metabolism, an increase of long-chain fatty acids, and possible dysregulation of the β-oxidation in older individuals. This is the first study on the molecular data set of normal human cardiac ageing, which, coupled with the innovative omics methods, enhances our understanding of the development of age-related heart diseases.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):