We humans have not evolved for optimal function given a continually high calorie intake. We, and all other species, evolved in an environment characterized by periods of feast and famine: we desire food constantly, but nonetheless need some amount of hunger in order to be healthy. Periods of low calorie intake spur increased activity of tissue maintenance mechanisms throughout the body. A lower overall calorie intake minimizes excess visceral fat tissue that causes chronic inflammation and metabolic disease. In this modern society of comfort and cheap calories, all too many people are eating themselves into shorter, less healthy lives. This will continue until the advent of rejuvenation therapies that can meaningfully target the causes of aging, to a degree sufficient to outweight environmental influences on the pace of aging.
The global increase in food security due to modern long-term food storage coupled with the increase in worldwide global food transportation, and international marketing has reduced the cost of food, increasing its availability in the developed world. However, food commercialization and the shift toward production of processed and ultra-processed foods have revealed clear adverse effects, such as the identification of processed food as a major cause for over-eating and the increase in the risk of metabolic syndrome, obesity, and diabetes. As the brain is one of the primary energy-demanding organs in the human body, it comes with no surprise that the brain is highly affected by such metabolic disorders.
Worldwide, the life expectancy of males rose from 59.6 years in the 1980’s to 69.0 years in 2015, whereas the life expectancy of females increased from 63.7 to 74.8 years, respectively. This increase in lifespan is correlated with multiple age-dependent pathologies which have also increased in prevalence, such as neurodegenerative disorders. It is plausible to argue that the combined effect of the continued increase in lifespan and life-long continuous food consumption leads to a dramatic increase in the prevalence of neurodegenerative disorders in the elderly population.
Studies in laboratory animals show that caloric restriction (decreased food intake or intermittent fasting) can extend lifespan in rodents and primates and delay the onset of age-related diseases such as hypertension and diabetes. Moreover, caloric restriction may protect neurons from degeneration and enhance adult neurogenesis and neuronal plasticity, which may protect the brain from a cognitive decline during aging and neurodegenerative diseases. One of the crucial processes that are adversely affected during aging is cellular autophagy, which is tasked with eliminating aggregated proteins, unhealthy organelles, and multiple intracellular components. Multiple mechanisms can explain the roles of fasting and caloric restriction in ameliorating neurodegeneration. One of the most studied mechanisms is the upregulation of autophagy via inhibiting mTOR activity.
The sobering statistics of one in three elderly people suffering from a type of age-related dementia call to devise a multi-pronged approach to targeting age-related neurodegenerative diseases. Synthesis of the current data indicates that not only age but also dietary lifestyles that changed dramatically during the twentieth century are at play. Many factors that are at play during aging have a role in promoting neurodegeneration, such as oxidative stress, accumulation of DNA damage, cell senescence, neuroinflammation, and decreased autophagic flux. Aging is also characterized by elevated levels of neuroinflammation that are transcriptionally regulated. Autophagy, however, is a cellular pathway that throughout life is predominantly regulated extrinsically in a nutrient-consumption mediated manner. This places food consumption as a major factor, along with aging itself, in promoting neurodegenerative disorders.