Aged Lymphatic Contractility: Recent Answers and New Questions

Abstract

An overview is presented of recent findings related to biology of aging of the lymph transport system. The authors discuss recently obtained data on the aging-associated alterations of lymphatic contractility in thoracic duct and mesenteric lymphatic vessels; on comparisons of function of aged mesenteric lymphatic vessels in situ versus isolated specimens and important conclusions which arose from these studies; on aging-associated changes in functional status of mast cells located close to aged mesenteric lymphatic vessels; on evidence of presence of oxidative stress in aged lymphatic vessels and changes in arrangement of muscle cells in their walls. The authors conclude that future continuation of the research efforts in this area is necessary and will be able to provide not only novel fundamental knowledge on the biology of lymphatic aging, but also will create solid foundation for the subsequent developments of lymphatic-oriented therapeutic interventions in many diseases of the elderly.T he major task of the lymphatic system is lymph transport. This system of initial capillaries, transporting vessels, and nodes is designed to transport fluid, soluble molecules, and immune cells from the interstitium through the lymph nodes to the central veins. This system also provides the transportation route for inflammatory mediators, the products of tissue injury/destruction, foreign substances, and tumor cells. Dysfunctional lymph transport can result in a wide range of disturbances, including edema, altered immune cell trafficking, depressed immune function, and impaired lipid metabolism. The lack of knowledge on how aging affects lymphatic vessels certainly contributes to the situation when researchers and clinicians ignore lymph transport-related components of various diseases. Thus, investigation of the mechanisms affecting lymphatic contractile function during aging are extremely important for ongoing attempts to better understand the lymphatic system and to discover the pathogenesis and effective treatment of various aging-associated disorders.Until recently, there were no published reports on systematic studies on aging-associated changes in the active lymph pumps. Due to the profound difficulty of measuring lymph flow in vivo, there are only a few reports demonstrating the measurements of reduced lymph flow in aged animals. [1][2][3] In particular, it was reported 3 that aging significantly decreases lymph flow from the main mesenteric lymph duct by *60% between ages of 3 and 22 mo in rats.During the last years, we obtained important functional and molecular evidence of the aging-associated alterations of contractility in lymphatic vessels, which already widened our knowledge on the biology of aged lymph flow. On the other hand, our recent studies raise new important questions that may link several diseases to impaired coordination between lymphatic function and function of other systems in the aged body. While this review provides some recent answers on current questions in biology of lymphatic aging,...

Hyperplasia, de novo lymphangiogenesis, and lymphatic regression in mice with tissue-specific, inducible overexpression of murine VEGF-D

“…In this capacity, lymphatics play a critical role in modulating tissue fluid balance and inflammation and provide a conduit for endocrine and lipid transport (27,34,37). Changes in lymphatic vessel architecture, integrity, and function have been described and implicated in congenital and acquired conditions of aging, inflammatory disease, lymphedema, and lipedema (12,13,23,24,50). Lymphangiogenesis, the growth of new lymphatic vessels, has been proposed as a potential therapy to many of these conditions, but is also a characteristic pathological response to inflammation, tumor progression, and chronic lymphatic-related diseases, such as lymphangioleiomyomatosis (35,53).…”

Mast Cell-Directed Recruitment of MHC Class II Positive Cells and Eosinophils Towards Mesenteric Lymphatic Vessels in Adulthood and Elderly

“…1 Aging creates several challenges to the lymphatic system by altering microenvironment 2 and ultrastructure 3 of lymphatic vasculature, which may create additional challenges to lymph flow and related functions mentioned above during various disease states. 4,5 Aging is associated with impaired lymphatic pumping with a significant decrease in frequency of spontaneous contractions and therefore a consequent decrease in minute productivity of lymphatic vessels. 6,7 Aging causes ''immunosenescence'' that contributes to increased mortality and morbidity in the aged population.…”

Emerging trends in the pathophysiology of lymphatic contractile function

“…In thoracic duct segments from older rats, lower lymphatic tone together with decreased lymphatic contraction amplitude may be considered an indicator of age-related weakening of muscle cells and their diminished ability to generate enough force to maintain the level of tone and contractile force appropriate to the lymphatic preload [138, 139]. The ability of the aged thoracic duct to adapt its pumping to different levels of extrinsic lymph flow is also severely altered.…”

“…In fact the eNOS-mediated imposed flow-dependent regulatory mechanism was completely depleted in 24-month-old thoracic duct segments [137]. Aging-associated weakening of the lymphatic pump has also been observed in mesenteric lymphatic vessels and it is proposed that aging remarkably weakens mesenteric lymphatic vessel contractility, which would predispose this lymphatic network to lower total lymph flows under resting conditions and limit its ability to respond to edemagenic challenges in the elderly [138, 139]. Aging has also been shown to significantly affect the muscle investiture of collecting lymphatics [140].…”