अल्जाइमर रोग और पार्किंसनिज्म जर्नल

अमूर्त

Evolutionary Considerations on Aging and Alzheimer's Disease

Armin Von Gunten, Marie-thérèse Clerc, Rahul Tomar and Paul St John-Smith

Increasingly people are surviving into old age both in high and middle/low income countries. The increase in longevity is associated with increased levels of morbidity of both somatic and mental disorders during those added years. These pathologies prompt developing strategies for effective prediction, prevention and treatment of such disorders, among them the dementias such as Alzheimer’s disease (AD). Aging lies on a temporal continuum that starts at conception and ends at death. It refers to the aging processes occurring during an individual’s lifetime. However, our understanding of aging remains limited. In the early stages of dementia, distinguishing normal from pathological aging remains complex. Medical research customarily investigates the immediate mechanisms or pathogenesis of “how” diseases come about and affect patients. Evolutionary perspectives consider the reasons “why” people may have become particularly vulnerable to different conditions. Examining why people age is illuminating. Around the question whether aging is adaptive, we consider some evolutionary concepts useful around aging theories, among others antagonistic pleiotropy and life history theory and more recent concepts including evolvability and evolutionary developmental biology. As AD seems to be specific to homo sapiens, its existence may in part be anchored in the adaptive changes that have occurred after the hominidae separated from the pongidae. Around the question why apparently non-adaptive conditions such as AD are so frequent, we consider, among other aspects, brain development including the related phenomena of altriciality and grandmothering, the evolution of ApoE and the genome lag hypothesis. We consider the idea that the neuropathological hallmarks of AD help mitigate neurodegeneration and cognitive decline rather than being its cause. Thus, an evolutionary look into AD may shed new light on the currently still sombre perspectives regarding disease-modifying treatments of AD and prove useful as a root cause analysis.