Motivation

Ageing is characterized by the gradual deterioration of an organism’s physiological ability to maintain, repair, and defend itself, increasing vulnerability to chronic and severe diseases [1].

The hallmarks of ageing, which drive the mechanisms underlying age-related diseases, are classified into three categories:

  1. primary hallmarks: causing cellular damage (i.e., genomic instability, telomere attrition, epigenetic alterations, proteostasis loss and disabled macroautophagy);
  2. antagonistic hallmarks: initially compensatory but later harmful (i.e., deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence);
  3. integrative hallmarks: driving ageing related functional decline (i.e., stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis) [2].

These hallmarks, either individually or in combination, contribute to the onset of various age-related diseases. For instance, heart failure is closely linked to cardiomyocyte senescence, primarily driven by oxidative stress. Mitochondrial dysfunction also plays a key role in reducing fatty acid β-oxidation, contributing to nonalcoholic fatty liver disease. While senescent cells act as a natural barrier to tumorigenesis due to their stable growth arrest, their persistence creates a chronic inflammatory and immunosuppressive microenvironment that promotes cancer development in the elderly [3].

Thera4Age project aligns with Saxony-Anhalt’s health and medical technology priorities, addressing key demographic and health challenges. While Germany’s increasing life expectancy is a significant achievement, Saxony-Anhalt has the lowest life expectancy among federal states (Figure 1) [4]. The state also has the highest average age due to migration and birth deficits [5], the greatest elderly dependency ratio (Figure 2) [6] and poor health among its ageing population [7]. Premature deaths (<70 years) are 30% above the national average [8], and in 2022, Saxony-Anhalt had Germany’s highest cancer mortality rate, 37% above the national average, mainly from digestive organ cancers, disproportionately affecting seniors [9].

Figure 1. Saxony-Anhalt has the lowest life expectancy in Germany (left: female, right: male) [4]

Figure 2. Elderly dependency ratio in Germany in 2023 [6]

Age-related diseases are also linked to reduced patient mobility, which increases the demand for care services and places significant financial strain on social systems. Consequently, current research efforts should focus on reducing morbidity and mortality through targeted, innovative therapeutic options [1]. As the global population continues to age and old-age dependency rises (Figure 3) [10], the interdisciplinary, translational, and innovative outcomes of the Thera4Age project will play a crucial role in addressing these pressing global challenges.

Figure 3. Interactive map of global elderly dependency ratio in 2023 [10]

  1. Tenchov R, Sasso JM, Wang X, Zhou QA. Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement. ACS Chem Neurosci. 15(1):1-30, 2024.
  2. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 186(2):243-278, 2023.
  3. Guo J, Huang X, Dou L, Yan M, Shen T, Tang W, Li J. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Sig Transduct Target Ther. 7:391, 2022.
  4. Durchschnittliche Lebenserwartung bei der Geburt, 2021-23, Statista, Stat Bundesamt.
  5. Durchschnittsalter der Bevölkerung in Deutschland nach Bundesländern 2023, Statista, Stat Bundesamt.
  6. Altenquotient in Deutschland nach Bundesländern im Jahr 2023, Statista, Stat Bundesamt.
  7. Gesamtmorbiditätsindex für Deutschland nach Bundesländern im Jahr 2022, Statista, Stat Bundesamt.
  8. https://www.statistikportal.de/de/nachhaltigkeit/ergebnisse/ziel-3-gesundheit-und-wohlergehen/vorzeitige-sterblichkeit accessed on 18.12.2024.
  9. Sachsen-Anhalt blieb 2022 weiterhin das Bundesland mit der höchsten Krebssterberate, Pressemitteilung, Nr. 26/2024, Halle (Saale), 2. Februar 2024, Stat Landesamt.
  10. The ratio of the elderly all population (ages 65 and over) to the working-age all population (ages 15 to 64). UN, World Population Prospects (2024) – processed by Our World in Data, https://ourworldindata.org/grapher/age-dependency-ratio-old?time=2023, accessed on 18.12.2024.
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