Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age-matched offspring of non-long-lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro- and anti-inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence of stroke, cerebral thrombosis-hemorrhage, hypertension, hypercholesterolemia, and other minor diseases, lower BMI and waist circumference, a better functional and cognitive status and lower plasma level of FT4 compared to NCO controls. We conclude that a multidimensional approach is a reliable strategy to identify the health status of elderly at an age when interventions to modify their health trajectory are feasible.