Read More at Fight Aging! While early senolytic therapies to clear senescent cells do well in mice, clearing a third to a half of the lingering senescent cells in some tissues and rapidly reversing many aspects of aging, to go much further than this will require a greater understanding of cellular senescence. Unfortunately, it is becoming clear that what we call senescence varies considerably from cell type to cell type, and there is much yet to be discovered regarding targets for therapy, ways to assess the burden of senescence, and more. Despite significant advances in the characterization of senescent cells (SnCs), many questions about the biology of these cells remain open. Firstly, it is necessary to understand which markers are necessary and sufficient to define that a cell is in a “full” or “deep” senescent state. Similarly, the dynamics and…
Cellular Senescence in Vascular Smooth Muscle Accelerates Medin Aggregation
Read More at Fight Aging! Medin is one of a number of different amyloids that form in aging tissue, each a protein that can misfold in ways that encourage other molecules of the same protein to do the same, aggregating together to form solid deposits. Some amyloids are evidently toxic and disease-associated, while others, like medin, originally appeared more innocuous. It isn’t harmless, however, just more subtle. Recent research suggested a pathological role for medin amyloid in Alzheimer’s disease, in that it accelerates the aggregation of amyloid-β. Further, there is evidence for medin aggregation to contribute to cerebrovascular dysfunction. On that topic, researchers here note that cellular senescence in the vascular smooth muscle of blood vessel walls can provoke greater medin aggregation in that tissue, providing a link between those two distinct mechanisms of aging. Vascular amyloidosis, caused when peptide…
Investigating PGE2, Cellular Senescence, and Macrophage Function in the Aging Lungs
Read More at Fight Aging! Researchers here show that blocking increased PGE2 signaling in the aging lung helps to restore resistance to influenza infection. There is an interaction between PGE2, cellular senescence in cells of the alveoli in the lung, and the behavior of local macrophages of the innate immune system. It remains to be seen whether PGE2 signaling is regulating much the same issues connected to cellular senescence elsewhere in the body. Previous research by another group showed that when macrophages from an old mouse were put into a young mouse, and cells looked young again. Signs pointed to a lipid immune modulator known as prostaglandin E2 (PGE2) with wide ranging effects. The study team discovered there is more PGE2 in the lungs with age. This increase in PGE2 acts on the macrophages in the lung, limiting their overall…
Cellular Senescence Contributes to Lung Aging
Read More at Fight Aging! Senescent cells accumulate in tissues throughout the body with age, the lung included, as noted here. This accumulation is thought to be largely the result of the progressive failure of the immune system to destroy newly created senescent cells in a timely fashion. These cells secrete a mix of signals that disrupts tissue structure and function, provoking chronic inflammation. Senolytic therapies capable of selectively destroying senescent cells have shown considerable promise in animal studies, reversing many aspects of aging and age-related disease. Senescent cells actively maintain a degraded state of tissue, and getting rid of them allows some degree of regeneration and restoration of lost function – a true rejuvenation therapy. Aging results in systemic changes that leave older adults at much higher risk for adverse outcomes following respiratory infections. Much work has been done…
Chromatin Structure in Cell Aging and Senescence
Read More at Fight Aging! The constantly changing structure of nuclear DNA, packaged into chromatin, determines which genes are accessible to the machinery of gene expression, which determines protein production, which determines cell behavior and state. Chromatin structure and all of the determinants of that structure, including epigenetic marks such as DNA methylation, change as a cell ages towards the Hayflick limit and cellular senescence, and change in aged tissues versus young tissues. Given the advent of epigenetic reprogramming as a potential strategy for rejuvenation, questions regarding the ways in which epigenetics determines cell function in cellular senescence and aging become more pressing. Comprehending the role of molecular processes such as DNA damage repair, telomere shortening, nuclear and chromatin changes along with epigenetic alterations which drive aging as well as aging related diseases may hold a key to the “elixir…
Inflammation and Cellular Senescence in the Aging Lung
Read More at Fight Aging! Here, researchers discuss what is known of the role of senescent cells, and the chronic inflammation that they create, in the aging of the lung. The first human trials of senolytic therapies to selectively destroy senescent cells were aimed at reversal of idiopathic pulmonary fibrosis. There is a good evidence for the growing presence of senescent cells to disrupt tissue maintenance and produce fibrosis as a result, the deposition of excessive, scar-like collagen structures that harm tissue function. There is a little that can be done to reverse fibrotic disease in the clinic, but animal studies showing improvement following clearance of senescent cells have given some hope for progress on this front. Cellular senescence, a coordinated cellular response to stress characterized by permanent cell cycle exit and the development of an elaborate secretory profile, is…