Molecular mechanisms underlying lineage bias in aging hematopoiesis

Elias, Harold; Bryder, David; Park, Christopher Y.

doi:10.1053/j.seminhematol.2016.11.002

Cited by 68 publications

(57 citation statements)

References 125 publications

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“…Senescent nonimmune cells secrete inflammatory mediators [57] which might be a significant source of chemokines and cytokines in tissues with aging. The aging process also affects the hematopoietic stem cells expanding the lineages of myelopoiesis and downregulating those of lymphopoiesis [102]. This myeloid-biased shift promotes the generation of myeloid cells in bone marrow and subsequently enhances their recruitment into aging tissues.…”

Section: Chronic Inflammation Is a Hallmark Of Aging Process And Alzhmentioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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The endoplasmic reticulum (ER) contains stress sensors which recognize the accumulation of unfolded proteins within the lumen of ER, and subsequently these transducers stimulate the unfolded protein response (UPR). The ER sensors include the IRE1, PERK, and ATF6 transducers which activate the UPR in an attempt to restore the quality of protein folding and thus maintain cellular homeostasis. If there is excessive stress, UPR signaling generates alarmins, e.g., chemokines and cytokines, which activate not only tissue-resident immune cells but also recruit myeloid and lymphoid cells into the affected tissues. ER stress is a crucial inducer of inflammation in many pathological conditions. A chronic low-grade inflammation and cellular senescence have been associated with the aging process and many age-related diseases, such as Alzheimer's disease. Currently, it is known that immune cells can exhibit great plasticity, i.e., they are able to display both pro-inflammatory and anti-inflammatory phenotypes in a context-dependent manner. The microenvironment encountered in chronic inflammatory conditions triggers a compensatory immunosuppression which defends tissues from excessive inflammation. Recent studies have revealed that chronic ER stress augments the suppressive phenotypes of immune cells, e.g., in tumors and other inflammatory disorders. The activation of immunosuppressive network, including myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), has been involved in the aging process and Alzheimer's disease. We will examine in detail whether the ER stress-related changes found in aging tissues and Alzheimer's disease are associated with the activation of immunosuppressive network, as has been observed in tumors and many chronic inflammatory diseases.

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Section: Chronic Inflammation Is a Hallmark Of Aging Process And Alzhmentioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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“…These studies clearly describe the cell-intrinsic HSC alterations that lead to aging-related hematopoietic deficiencies. While the cell-autonomous changes in the HSC that promote aging-related changes in hematopoiesis are more well defined, the contribution of the aged bone marrow (BM) microenvironment in promoting aged hematopoietic phenotypes is poorly understood (16,17).…”

Section: Introductionmentioning

confidence: 99%

Endothelial transplantation rejuvenates aged hematopoietic stem cell function

Poulos¹,

Ramalingam

Gutkin

et al. 2017

Journal of Clinical Investigation

127

105

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“…While aging and lifespan involve multiple physiological pathways (Kirkwood and Austad 2000; Warren and Rossi 2009) from molecular to intercellular (López-Otín et al 2013), hematopoiesis in its position at the top of the immune system, plays a central role in immune system aging (Geiger et al 2013), immunosenescence and of somatic tissue deregulation (Henry et al 2011; Kovtonyuk et al 2016; Park 2017). Aging in these systems can lead to proximal causes of mortality such as cancer (Rozhok et al 2014; Rozhok and DeGregori 2016) and chronic stress that feed back to increase leukocyte production resulting in atherosclerosis, inflammation and cardiovascular disease (Hanna and Hedrick 2014; Heidt et al 2014; Elias et al 2017). Also, the sympathetic nervous system regulates the HSC self-renewal rate, pool size and the rate blood cells egress to the circulation system (Bellinger and Lorton 2014).…”

Section: Methodsmentioning

confidence: 99%

The relationship of mammal survivorship and body mass modeled by metabolic and vitality theories

Anderson¹

2018

Population Ecology

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A model describes the relationship between mammal body mass and survivorship by combining replicative senescence theory postulating a cellular basis of aging, metabolic theory relating metabolism to body mass, and vitality theory relating survival to vitality loss and extrinsic mortality. In the combined framework, intrinsic mortality results from replicative senescence of the hematopoietic stem cells and extrinsic mortality results from environmental challenges. Because the model expresses the intrinsic and extrinsic rates with different powers of body mass, across the spectrum of mammals, survivorship changes from Type I to Type II curve shapes with decreasing body mass. Fitting the model to body mass and maximum lifespan data of 494 nonvolant mammals yields allometric relationships of body mass to the vitality parameters, from which full survivorship profiles were generated from body mass alone. Because maximum lifespan data is predominantly derived from captive populations, the generated survivorship curves were dominated by intrinsic mortality. Comparison of the mass-derived and observed survivorship curves provides insights into how specific populations deviate from the aggregate of populations observed under captivity.

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Molecular mechanisms underlying lineage bias in aging hematopoiesis

Cited by 68 publications

References 125 publications

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

Endothelial transplantation rejuvenates aged hematopoietic stem cell function

The relationship of mammal survivorship and body mass modeled by metabolic and vitality theories

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