Pharmacologic and environmental modulation of biological aging

Pharmacological Sciences

Host Department
Department of Pharmaceutical and Pharmacological Sciences

Research Topic A

Abstract of the proposed UNIPhD research project

Sarcopenia is a progressive systemic skeletal muscle problem that causes significant health concerns due to muscle instability and durability degradation (1). The World Health Organization (WHO) has identified sarcopenia as a serious threat and risk factor for several age-related diseases (2). Physical impairment and the inability to manage daily activities lower the patient’s quality of life and increase the patient’s need for long-term care services (3).

According to research, birth weight is associated with adult muscle mass, muscle metabolism, and muscle strength (4,5). Epidemiological studies have shown that low birth weight has a negative impact on muscular strength (6). Furthermore, recent studies reported that mitochondrial generation of reactive oxygen species(ROS) in skeletal muscle has been shown to increase with age, which could explain the increment in mtDNA mutations related to sarcopenia in elderly skeletal muscles (7).

The project will focus on the effect of body mass at birth on sarcopenia in adult and premature aging. Individuals born small will be used to investigate the reduced muscle weakness in adults. Human-based studies will include both young and old participants and birth weights less than 3.0 kg will be connected to accelerated biological ageing and sarcopenia. People will be evaluated including parameters of body composition analysis, muscle strength testing, sarcopenia diagnosis and classification (non-sarcopenic, pre-sarcopenic, sarcopenic and severely sarcopenic). Sarcopenia will be identified in accordance with the EWGSOP2 criteria and using the latest ultrasound sarcopenia index. Biological aging will be evaluated by exploring the cellular mitotic leukocyte TL(LTL) and epigenetic age(DNAmAge), and the nuclear-mitochondrial axis, including p53 expression and mtDNA copy number(mtDNAcn). Subjects will be further characterised using the 15 susceptibility loci, identified in the genome-wide meta-analysis, to explore the genetic susceptibility of muscle weakness. We will be able to determine how soon these ageing effects can occur by monitoring early molecular markers of cellular ageing and sarcopenia conditions at different stages of a person’s life.

Sarcopenia is an important increasing problem for older people across the world due to ageing and environmental factors and more research is necessary to address the disease in many aspects. Early detection of risk factors can eliminate many of the negative consequences. The findings of the project will be beneficial for future therapeutic research. Once disease-associated genetic variations are identified, they can be used to detect and monitor populations to practise preventative medicine (8).
References
1. Musumeci, G. Sarcopenia and exercise “the state of the art.” Journal of Functional Morphology and Kinesiology vol. 2 Preprint at https://doi.org/10.3390/jfmk2040040 (2017).
2. Gustafsson, T. & Ulfhake, B. Sarcopenia: What Is the Origin of This Aging-Induced Disorder? Frontiers in Genetics vol. 12 Preprint at https://doi.org/10.3389/fgene.2021.688526 (2021).
3. Giovannini, S. et al. Sarcopenia: Diagnosis and management, state of the art and contribution of ultrasound. Journal of Clinical Medicine vol. 10 Preprint at https://doi.org/10.3390/jcm10235552 (2021).
4. Gale, C. R., Martyn, C. N., Kellingray, S., Eastell, R. & Cooper, C. Intrauterine Programming of Adult Body Composition*. The Journal of Clinical Endocrinology & Metabolism Printed vol. 86 https://academic.oup.com/jcem/article/86/1/267/2841201 (2001).
5. Garay, J. L., Barreira, T. v., Wang, Q. & Brutsaert, T. D. Intra-uterine effects on adult muscle strength. Early Human Development 163, (2021).
6. Dodds, R. et al. Birth weight and muscle strength: a systematic review and meta-analysis.
7. Marzetti, E., Lees, H. A., Wohlgemuth, S. E. & Leeuwenburgh, C. Sarcopenia of aging: Underlying cellular mechanisms and protection by calorie restriction. BioFactors vol. 35 28–35 Preprint at https://doi.org/10.1002/biof.5 (2009).
8. di Renzo, L. et al. Individually tailored screening of susceptibility to sarcopenia using p53 codon 72 polymorphism, phenotypes, and conventional risk factors. Disease Markers 2014, (2014).

Short bio

Dilek Celik is a UNIPhD doctoral fellow in Pharmacological Sciences at the University of Padua. She is particularly interested in understanding the role of genetic factors in addition to environmental/lifestyle factors in epidemiology of diseases and understanding molecular perspectives in epidemiology. Her area of research is pharmacologic and environmental modulation of biological ageing. Her research project seeks to investigate the epigenetic basis for how low birth weight affects the plausibility of developing sarcopenia in older age. Throughout the project, early molecular markers of cellular ageing and sarcopenia conditions will be monitored at different periods of a person’s life to determine how early ageing effects can occur.