Macrophage function in the elderly and impact on injury repair and cancer

Duong, Lelinh; Radley‐Crabb, Hannah G.; Lee, B; Dye, DE; Pixley, Fiona J.; Grounds, Miranda D.; Nelson, D. C.; Jackaman, Connie

doi:10.1186/s12979-021-00215-2

Cited by 55 publications

(36 citation statements)

References 144 publications

(212 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also, expansion of the staining panels with, for example, phenotypic markers to improve CD8 + T cell gating, could also be considered in future studies. Furthermore, other innate signaling cytokines such as IL-4 and IL-8 could be considered to be included, especially since the function of myeloid lineage cells is thought to become impaired with age [ 5 , 49 ] and numbers of myeloid cells are higher in frail older people [ 31 ]. Lastly, how the results translate to in-vivo signaling remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Impaired JAK-STAT pathway signaling in leukocytes of the frail elderly

et al. 2022

View full text Add to dashboard Cite

Background Elderly often show reduced immune functioning and can develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with altered cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65–74 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Presence of chronic low-grade inflammation was investigated by evaluating 18 different plasma inflammatory markers that had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and women, indicative of dysfunctional pSTAT responses in frailer individuals. Associations differed between men and women, with frailer women showing lower pSTAT1 responses in monocytes and frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells. Notably, lower IL-10-induced pSTAT3 responses in men were related to both higher frailty scores and higher CRP levels over the past 20 years. This might indicate poor resolution of low-grade inflammation due to defective regulatory pSTAT signaling in older men. Conclusions Our results emphasize the importance of preserved JAK-STAT pathway signaling in healthy aging and reveal cellular pSTAT levels as a candidate biomarker of frailty.

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired JAK-STAT pathway signaling in leukocytes of the frail elderly

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Larger phospho-ow panels may give a more complete description of cellular responsiveness in frail older people. Other innate signaling cytokines such as IL-4 and IL-8 could also be considered in future studies, especially since the function of myeloid lineage cells is thought to become impaired with age (4,42) and numbers of myeloid cells are higher in frail older people (27). Also, how the results translate to in-vivo signaling remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Impaired JAK-STAT Pathway Signaling in Leukocytes of Frail Elderly

Samson

Engelfriet

Picavet

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Elderly often show reduced immune functioning and develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with differences in cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65-77 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Plasma inflammatory markers had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results: We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and women, indicative of dysfunctional pSTAT responses in frailer individuals. Associations differed between men and women, with frailer women showing lower pSTAT1 responses in monocytes and frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells. Notably, lower IL-10-induced pSTAT3 responses in men were related to both higher frailty scores and higher CRP levels over the past 20 years. This might indicate poor resolution of low-grade inflammation due to defective regulatory pSTAT signaling in older men. Conclusions: Our results emphasize the importance of preserved JAK-STAT pathway signaling in healthy aging and reveal cellular pSTAT levels as a candidate biomarker of frailty.

show abstract

“…ere is early infiltration of neutrophils but delayed infiltration of monocytes-macrophages compared to the young population. Macrophages played an important role in wound healing, and their late infiltration may be one reason for impaired wound healing in this population [78]. In rat models, angiogenesis is reduced in aged rats [79] and has reduced macrophage content [80].…”

Section: Uremia and Renal Dysfunctionmentioning

confidence: 99%

Mammalian Target of Rapamycin Inhibitors and Wound Healing Complications in Kidney Transplantation: Old Myths and New Realities

Khalil

Al-Ghamdi

Dawood

et al. 2022

Journal of Transplantation

View full text Add to dashboard Cite

Mammalian target of rapamycin inhibitors (mTOR-I) lacks nephrotoxicity, has antineoplastic effects, and reduces viral infections in kidney transplant recipients. Earlier studies reported a significant incidence of wound healing complications and lymphocele. This resulted in the uncomfortable willingness of transplant clinicians to use these agents in the immediate posttransplant period. As evidence and experience evolved over time, much useful information became available about the optimal use of these agents. Understandably, mTOR-I effects wound healing through their antiproliferative properties. However, there are a lot of other immunological and nonimmunological factors which can also contribute to wound healing complications. These risk factors include obesity, uremia, increasing age, diabetes, smoking, alcoholism, and protein-energy malnutrition. Except for age, the rest of all these risk factors are modifiable. At the same time, mycophenolic acid derivatives, steroids, and antithymocyte globulin (ATG) have also been implicated in wound healing complications. A lot has been learnt about the optimal dose of mTOR-I and their trough levels, its combinations with other immunosuppressive medications, and patients’ profile, enabling clinicians to use these agents appropriately for maximum benefits. Recent randomized control trials have further increased the confidence of clinicians to use these agents in immediate posttransplant periods.

show abstract

Macrophage function in the elderly and impact on injury repair and cancer

Cited by 55 publications

References 144 publications

Impaired JAK-STAT pathway signaling in leukocytes of the frail elderly

Impaired JAK-STAT pathway signaling in leukocytes of the frail elderly

Impaired JAK-STAT Pathway Signaling in Leukocytes of Frail Elderly

Mammalian Target of Rapamycin Inhibitors and Wound Healing Complications in Kidney Transplantation: Old Myths and New Realities

Contact Info

Product

Resources

About