The article focuses on estimating reserves of growth in life expectancy at birth (LEB) for the RF population in regions with different sanitary-epidemiological wellbeing and people’s lifestyles. The existing trends in the country development within the regional context corroborate relevance of the present study. The methodical approach includes use of factor and cluster analysis, artificial neuron networks, and scenario forecasting. Activities performed by Rospotrebnadzor within its authority produce positive modifying effects on LEB as an integral health indicator. Differentiated contribution made by these activities to achieving regional target LEB levels by 2024 (COVID-related processes excluded) amounts to 8–62 % as per the group of indicators that describes a sanitary-epidemiological situation on a given territory and 5–45 % as per the group of lifestyle-related indicators. We identified priority factors for each of four types of regions; these factors provide the maximum positive effect on LEB. Working conditions for working population, quality of drinking water, ambient air and nonfoods are priority manageable factors in regions where the sanitary-epidemiological situation is the most unfavorable. Levels of alcohol and food consumption, balanced diets and people’s physical activity are the priority manageable factors in regions with the most unfavorable lifestyle-related indicators. The study revealed that additional LEB growth would be secured if the targets set within national projects were achieved. By 2024, this additional LEB growth would equal 6–420 days and 107–659 days accordingly given the existing trends and regional differentiation as regards improved sanitary-epidemiological situation in regions and people’s lifestyles. Improved working conditions, better quality of drinking water and ambient air are reserves of LEB growth for all types of the RF regions in short and middle-term. A potential reserve of LEB growth and priority determinants were identified for each type of regions. These identified national and regional determinants should be considered when building an optimization model of LEB management allowing for reserves of its growth. The study results develop the authors’ methodical approach to estimating potential LEB growth based on scenario modeling; they are consistent with the results obtained by other relevant studies. We have identified limitations of the present study as well as prospects and trends for future research.