Aging successfully: The role of genetics and environment in the era of the aging-boom. potential therapeutic implications

Abstract

Aging is one of the main health-related challenges in the world. The average life expectancy of the global population at birth is increasing up to 72 years, in 2016 and it increases about two years every decade. The healthcare costs in many countries are very high because of the increased number of unhealthy populations, and the consequent increase of severe age-related disabilities [1]. Therefore, the goal of the future should be the achievement of the so-called “health-span” (healthy-life-span), more than the treatment of age-related disease to prevent the collapse of the health system. In order to achieve this objective, it is necessary to identify new targets and biomarkers and to address key issues of aging to delay or prevent the onset of pathologies and disorders. This would allow to develop or to identify anti-aging therapies, modulating aging rate, or tested known drugs for different uses (i.e. to reduce systemic or local inflammation). Aging is an ineluctable process, which affects all cells, tissues, organs, and organisms, narrowing the homeodynamic space and increasing organism vulnerability, although it has demonstrated in model organisms the possibility to modulate some pathways related to aging processes. Systemic aging causes a reduction in the response to environmental stimuli and, in general, is associated with an increased predisposition to disease and death. However, there are two ways to become old: without success (unsuccessful aging, UA) and with success (successful aging, SA) [2,3]. UA is manifested by people that develop one or more age-related diseases, such as neurodegenerative (Alzheimer’s or Parkinson’s disease), metabolic (metabolic syndrome and type 2 diabetes mellitus), cardiovascular, and cancer [2]. Regarding SA, the World Health Organization defines it as “the process of developing and maintaining the functional ability, which enables well-being in older age”, and defines healthy aging as “the process of developing and maintaining the functional ability, which enables wellbeing in older age” [3,4]. Thus, promoting healthy and successfully aging is a key priority, taking into account that this trait is heterogeneous and is influenced by genetic, epigenetic, and environmental factors. In adulthood, the heritability of age of death is approximately 25%, but it can reach even 48% in males who achieve exceptional longevity. Many of the genetic aspects of longevity include mutations or polymorphisms, which can occur at different frequencies within a population. Indeed, longevity genes affect a vast spectrum of biological functions that improve the feature of repair mechanisms, increase the resistance to stressors like virus and injury, and slow the age-related changes in cells and tissues. The remaining part is due to the environmental exposure, chance, stochastic events, access to health care, and lack of trivial accidents [5,6]. The correlation between genetic background and the environment in determining the individual chance of delayed aging or SA is an emerging topic in gerontology. Therefore, the proven and significant correlation between the effects of environment and molecular pathways may be used as preventive measures to increase the chance to attain longevity or health-span.