Therefore, reduced LTP linked to enhanced GABAA receptor-mediated inhibition may be triggered by aging and may be accelerated by familial AD-linked gene products like Aβ and mutant PS1, leading to cognitive decline that is pharmacologically treatable at least at this stage of disease progression in mice.
Although the link between neuroinflammation and AD pathology is now well recognized, how brain innate immunity is driven in AD is still a matter of debate – especially whether neuroinflammation can be triggered by age-related systemic inflammation [ 19].
The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by ageing-related processes in later life to cause the neuronal withering of Alzheimer's disease.
Moreover, endoplasmic reticulum stress was triggered by AGE-induced oxidative stress, resulting in the activation of C/EBP homologous protein (CHOP) and caspase-12 that consequently initiates cell death.
Human aging can be triggered by two main mechanisms, telomere shortening and DNA damage.
From work carried out in collaboration with Southampton researchers, John Hardy (UCL, UK) suggested that seeding of amyloid-beta (Aβ) plaques and propagation of tau could be triggered by loss of homoeostasis due to age-related failure of lymphatic drainage along walls of aged cerebral arteries.
The activation of p16 expression can be triggered by DNA damage, oncogenic stress or physiological aging [ 7].
More importantly, the non-neuronal release of activators can be triggered by inflammation, ischemia, and oxidative stress in aging and pathological conditions (38, 39).
Changes can be triggered by time alone (e.g. due to natural aging) or by events (e.g. occurrence of osteoporosis).
The bimodal distribution of the onset of seizures appears to be another marker of the age-associated alterations that might be triggered by biochemical and structural alterations [ 25].
Negative micro events can be triggered by any perception of difference (i.e., body type, socio-economic class, age) due to our unconscious biases.
