The heterogeneous approach to reach longevity: the experience of Italian centenarians

People reaching old age are increasing exponentially in recent decades, and centenarians represent the fastest-growing group. Aging is characterized by the continuous adaptation of the organism to life-long exposure to stress that leads to a relevant clinical complexity. It is reasonable to think that centenarians do not escape the physiological decline or the age-related diseases and syndromes, but the rate of such processes is slow enough to be counterbalanced by their increased capacity to respond to stresses. Therefore, depending on the ability of each person to respond suc-cessfully or unsuccessfully to stressors, the aging process changes, leading to extremely heterogeneous phenotypes, particularly evident among centenarians. In a cohort of Italian centenarians, the high heterogeneity in health status was well captured by means of the Frailty Index (FI) computed utilizing clinical variables. Surprisingly, in the same cohort, a FI computed utilizing biological variables showed average lower values and a narrower distribution than the clinical one. Interestingly, these centenarians showed higher blood free T4 (FT4) and thyroid-stimulating hormone (TSH) levels, and lower blood free T3 (FT3) levels and FT3/ FT4 ratio than younger persons. Moreover, their endocrine profile was characterized by high adiponectin levels and insulin sensitivity, and low insulin growth factor-1 (IGF-1) and leptin levels. Under these premises, studies on centenarians open a window to extreme longevity. Metabolic remodelling of these persons is suggestive of benefits that play a critical and positive role in shaping healthy aging.