Mitochondria are ancient endomembrane systems of eukaryotic cells with a well-recognised role in the production of ATP. However, research in the last decade has revolutionised the way in which we view mitochondria. Mitochondria are an interconnected network of organelles that are constantly involved in processes of fusion and fission to cope with cellular energy demand. Mitochondria also provide metabolic intermediates for the synthesis of macromolecules such as lipids, proteins and nucleotides. Moreover, mitochondria regulate numerous biological responses through reactive oxygen species generation and subsequent thiol oxidation and citrate export, which will be converted into acetyl-CoA used for protein lysine acetylation. Furthermore, mitochondria interact intimately with other cellular compartments, regulating their function. Ultimately, mitochondria emerge as signalling organelles essential to maintaining cellular homeostasis beyond ATP generation.

Cellular senescence entails a permanent cell cycle arrest, characterised by extensive changes in gene expression, a pro-inflammatory senescence-associated secretory phenotype (SASP), and apoptosis resistance. Physiologically, senescent cells promote tissue remodelling during development and after injury, but when accumulated over a certain threshold, as happens during ageing, contribute to the decline of the regenerative potential and function of tissues. Although the presence of senescent cells has been reported in aged brain tissue and in brain tissue from several neurodegenerative diseases, our knowledge of the role of senescence in the central nervous system remains limited. Mitochondrial function/dysfunction is often observed in neurodegenerative diseases that accompany ageing, such as Alzheimer’s disease and dementia. However, the current understanding regarding the role of mitochondrial function/dysfunction on senescence and its impact in the progression of these diseases is quite limited. Thus, comprehensive knowledge of the impact of mitochondria in senescence in the context of ageing and neurodegenerative diseases may be relevant to develop new therapeutic strategies.

The aim of this Special Issue is to gather research exploring the pivotal role of mitochondria on cellular metabolism in health and disease and the impact of senescence cells in ageing and neurodegeneration. We invite scientists to contribute original research as well as review articles ranging from basic science to clinical studies.

Potential topics include but are not limited to the following:

• Role of mitochondria in the establishment of senescence phenotype
• Mitochondrial dynamics and its impact in senescence
• Senescence in the central nervous system
• Role of senescence in neurodegeneration
• Metabolic Intervention in neurodegeneration and/or ageing and its impact in cellular senescence