Novel targets for delaying aging: The importance of the liver and advances in drug delivery

Age-related changes in liver function have a significant impact on systemic aging and susceptibility to age-related diseases. Nutrient sensing pathways have emerged as important targets for the development of drugs that delay aging and the onset age-related diseases. This supports a central role for the hepatic regulation of metabolism in the association between nutrition and aging. Recently, a role for liver sinusoidal endothelial cells (LSECs) in the relationship between aging and metabolism has also been proposed. Age-related loss of fenestrations within LSECs impairs the transfer of substrates (such as lipoproteins and insulin) between sinusoidal blood and hepatocytes, resulting in post-prandial hyperlipidemia and insulin resistance. Targeted drug delivery methods such as nanoparticles and quantum dots will facilitate the direct delivery of drugs that regulate fenestrations in LSECs, providing an innovative approach to ameliorating age-related diseases and increasing healthspan. (C) 2018 Elsevier B.V. All rights reserved.