Az élettartamot meghatározó exogén és endogén tényezők • Exogenous and Endogenous Factors Determining Lifespan

Abstract

Man is ‘condemned to die’ from the moment of his birth and must live with this fact. Life expectancy is influenced aspecifically by exogenous factors (natural disasters, wars, epidemics, accidents, social circumstances, criminal events, etc.), while endogenous factors (genetically en-coded within the organism) determine it. Ageing is characterised by a gradual loss of physiological integrity leading to deterioration of function and death. The literature identifies (1) genomic instability, (2) telomere loss, (3) mitochondrial dysfunction, (4) epigenetic alterations, (5) loss of proteostasis, (6) unregulated nutrient sensing, reduced autophagy, (7) cellular senescence, (8) stem cell exhaustion, and (9) altered intercellular communication as hallmarks of ageing. These ageing-related changes are associated with late-onset diseases such as neurodegenera-tive disorders, cardiovascular diseases, metabolic syndrome, and cancer. A less well known area of mitochondrial dysfunction is fibrosis in certain parenchymal organs. All these pathologies have a significant impact on life expectancy and quality of life. A central aim of research is to develop strategies to reduce age-related disease and vulnerability, reduce frailty, and improve quality of life in old age. In addition to genetic predisposition, lifestyle is a key player in achiev-ing long, healthy life expectancy. Among the possible interventions, calorie restriction (‘quality starvation’), regular exercise, and weight normalisation appear to be the most effective. Certain agents increase or pre-regulate autophagic activity and have been shown to be effective geroprotectors. The mTOR rapamycin system plays a key role in nutrient sensing. The target of rapamycin’s action is mTOR, whose inhibition mediates the effect of calorie restriction. Sirtuins modulate cell protective mechanisms such as defence against oxidative stress, DNA repair, en-ergy utilization, and autophagy. Metformin is a known antidiabetic drug, with recent focus on its potential use in prolonging healthy life span. Ageing is a natural physiological process of the body. It is the responsibility of the individual to pursue a healthy old age with dignity through lifestyle, and it is the responsibility of the health government of every country to support the longest possible healthy life span for all its citizens.