The following are generally accepted as the predominant root causes of degenerative disease and disease associated with ageing (Lopez-Otin et al. 2013, Schmauch-Medina et al. 2022, Tower 2015, Maldonado et al. 2023).
They result in impaired organ function & disease, cell death, tissue damage, oxidative stress, and accumulation of damaged molecules & cell machinery, highlighting the need for multifaceted interventions.
Key Root Causes of Age-Associated Disease
Failure of resident stem cell populations
Senescent cell accumulation
Necrosis
Inflammation
Failure of Autophagy
Oxidative damage
Mitochondrial dysfunction
These root causes of pathology represent cellular and molecular mechanisms that contribute to ageing and chronic disease. Failure of resident stem cell populations and senescent cell accumulation result in reduced tissue regeneration and repair, leading to impaired organ function and disease. Necrosis and inflammation are linked to cell death and tissue damage, which can accelerate ageing and lead to chronic diseases such as arthritis and neurogenerative conditions. Failed autophagy and mitochondrial dysfunction also contribute to the accumulation of damaged molecules and cell machinery, resulting in oxidative stress and inflammation, in turn accelerating ageing and disease. These issues, and the associated age-related diseases they lead to, highlight the need for multifaceted interventions that target multiple hallmarks of ageing and wider degenerative conditions.