Ateneo - UPO

Critical analysis of the hallmarks of aging and associated biomarkers that can be used for diagnostic, prognostic and therapeutic purposes: 1) the main molecular pathways involved in genomic stability, proteostasis and oxidative stress; 2) the role of senescence in aging and age-associated diseases; 3) the metabolic pathways involved in energy homeostasis; 4) the biomarkers of biological aging; 5) the main metabolic alterations associated with accelerated aging.

Slides and other didactic material provided by the teacher; scientific papers discussed during classes; online public database resources.

The growth of the older population increases prevalence rates of non-communicable diseases and of old-age disability, creating demands that many health systems are currently not equipped to meet. The main objective of the course is providing the basic knowledge about the molecular pathways involved in aging for the identification of molecular determinants predictive of healthy or unhealthy aging and biomarkers with predictive, diagnostic or therapeutic implications for age-associated diseases.

The students are expected to have a general knowledge of biochemistry, molecular biology and genetics and of the main technologies used in genomic investigations

Slides presented during the course, interactive scientific papers discussion; PDF copy of scientific papers

All the teaching material and information regarding the course will be available on Moodle Platform (DIR; https://www.dir. uniupo. it/)

Evaluation will consist in a written test which includes multiple choice questions and open questions that will allow to evaluate learning about the topics covered during the course.
Detailed program of the course and information regarding the final exam will be available on Moodle Platform (DIR; https://www.dir. uniupo. it/)

1_Aging statistics. Population aging in different countries. The demographic transition. The speed of population aging. The burden of chronic non communicable diseases. The life course approach to health. WHO key determinants for active/healthy aging.
2_The hallmarks of aging. Molecular definition of aging. Definition of “hallmark of aging” and their functional interconnections. Brief description of the hallmarks of aging: genomic and mitochondrial DNA instability; telomers attrition; epigenetic modifications; deregulation of nutrient sensing; cellular senescence; stem cell exhaustion; altered intercellular communication, inflammaging; mitochondrial disfunction
3_Genomic instability: Consequences of mutation on genes and protein functions. Functional consequences of genomic alterations: proliferative advantage, somatic mosaicism and aberrant clonal expansion, cancer and neurodegenerative disorders. Mitochondrial DNA alterations.
4_Epigenetic modifications. The epigenetic clock. DNA methylation profiling to prdict lifespan and healthspan.
5_Senescence. Types of senescence; causes of senescence; molecular pathways associated with senescence; paracrine and endocrine effects of SASP; senolitics and aging
6_Proteostasis. Definition of proteostasis network. The chaperones HSP70, HSP90, chaperonins: main characteristics and functions. The HSF1 response. Protein degradation by proteasome and autophagy, the chaperons mediated autophagy. ER stress and Unfolded Protein Response (UPR). The proteins aggregates and amyloid fibrils
7_Oxidative stress. The concept of oxidative stress, eustress and distress. The concept of hormesis in oxidative stress. The main reactive species, radicals and nonradicals, structure and characteristics: ROS, RNS, reactive carbonyl species. The backbone role of NAD/NADH and NADP/NADPH systems in redox homeostasis. The role of the energy-linked nicotinamide nucleotide transhydrogenase (NNT). The main sources of ROS. The Haber-Weiss / Fenton reaction. The ROS scavenging system: peroxiredoxin/thioredoxin system, the glutathione system, SOD, catalase.
Eustress. The redox code. The thiol/disulfide systems. Role of H2O2 in redox signalling: peroxiporins. The ROS/Keap1-NRF2 and NF-kB pathways. The NOX family of ROS generating NADPH oxidases. Hints of redox signalling
Molecular and cellular alterations promoted by oxidative stress. Lipid peroxidation. Reactive aldehydes: structure and activity. Protein damage by oxidative distress. Protein damage by oxidative distress: protein carbonylation and thiol group oxidation. DNA damage and DDR (DNA damage Repair) pathways; structure of oxoguanine; common oxidized pyrimidines. Susceptibility of telomeres to oxidative damage. The OGG1-BER pathway. Role of PARP1 in DNA repair downstream oxidative stress. The nonenzymatic antioxidants: vit. C, vit E, vit. A, bioflavonoids, carotenoids. Physiological antioxidants.
8_Altered intercellular communication: inflammaging. Inflammaging and immunosenescence, causes of inflammaging; nutrient sensing and inflammaging; mataflammation; adipose tissue and inflammaging; ER stress and inflammaging; insulin resistance and inflammaging.
9_Nutrient and energy sensing. Insulin signaling and metabolic effects of insulin, alteration in insulin signaling, obesity and T2D. AMPK and mTOR pathways in the regulation of catabolic and anabolic processes; caloric restriction and aging

At the end of the course students will gain a deeper understanding of the hallmarks of aging and their role in the aging process and in the pathogenesis of the most frequent aging-associated diseases, such as cancer and metabolic disorders. Students will be able to evaluate the molecular pathways underlying aging and identify potential biomarkers of biological aging to translate into predictive, diagnostic or therapeutic opportunity both in basic and translational research and in a care setting. The acquired knowledge can also be used in epidemiological studies and prevention interventions