Aging is a natural process. As we grow older, everyone will age slowly, which seems to be an unchangeable natural law. However, in recent years, with the acceleration of global aging, countries around the world have set off a wave of anti-aging research, and various anti-aging drugs and therapies have been discovered one after another, such as nicotinamide , metformin and Senolytics therapy.
Senescent cells will continue to exist and continue to secrete many pro-inflammatory and tissue remodeling molecules to poison other surrounding cells. Not only that, scientists used transcriptome analysis to find that, like cancer cells, senescent cells increase the expression of "pro-survival networks", thereby helping them resist apoptosis or programmed cell death.
In 2015, Dr. James Kirkland , et al. of Mayo Medical Center in the United States, published a paper in the Aging Cell journal 【1】, reporting a drug combination of selectively killing senescent cells —Senolytics. Senolytics therapy composed of dasatinib and quercetin may be able to selectively induce senescent cell death. Among them, dasatinib can remove aging human adipocyte progenitor cells, while quercetin can kill aging human endothelial cells and mouse bone marrow stem cell . The combination of the two is more effective.
From this point of view, senescent cells are the key driver of the body's aging, and clearing senescent cells can delay or alleviate many age-related diseases . But it is obvious that aging drugs have difficulty removing all senescent cells. Therefore, it remains a critical question to identify which senescent cell type has the greatest effect on aging and to use it as the most preferred therapeutic target.
Recently, researchers from the University of Minnesota School of Medicine published a research paper entitled: An aged immuno system drives sensing and ageing of solid organs in the top international academic journal Nature .
This study shows that aging immune cells is the most dangerous type of senescent cell, which will accelerate the aging of other organs and promote systemic aging . Therefore, aging immune cells have also become a key therapeutic target for extending healthy lifespan.
For most chronic diseases, its incidence rate is closely related to age. During aging, the immune system loses the ability to respond effectively to pathogens and cancer cells. This decline in immune function is known as immune aging, characterized by changes in naive memory T cell ratios, CD4:CD8 ratios, impaired calcium-mediated signaling and thymus atrophy.
In addition, many immune cell types will continue to age, with increased levels of expression of p16INK4a (CDKN2A) and p21CIP1 (CDKN1A) and , as well as aging-related secretory phenotype (SASP) . These age-related changes limit the effectiveness of the vaccine, increase the susceptibility to the disease, and lead to mortality in older adults.
Previous studies have found that reducing the expression of ERCC1-XPF endonuclease in experimental mice will disrupt the repair of DNA damage and accelerate the accumulation of endogenous oxidative damage and senescent cells in a variety of tissues in mice, which leads to premature onset of diseases and histopathology related to mouse and human aging.
Therefore, in this study, in order to clarify the contribution of immune system aging to body aging, the research team selectively deleted the Ercc1 gene in mouse hematopoietic cells, thereby only increasing the burden of endogenous DNA damage in the immune system and causing immune cell aging.
Researchers found that these mice showed premature occurrence of immune aging after healthy development into adulthood, characterized by loss and aging of specific immune cell populations and impaired immune function, and similar to changes occurring in wild-type mice during aging.
The deletion of Ercc1 in hematopoietic cells will lead to accelerated aging of the immune system
It is worth noting that non-lymphological organs of these mice that deleted the Ercc1 gene also showed an increase in aging and damage, suggesting that aging immune cells can promote systemic aging. In addition, the researchers transplanted spleen cells from these knockout mice or elderly wild-type mice to young mice, which also accelerated the latter's aging.
The aging immune system drives the aging of non-lymphological organs and the loss of tissue homeostasis
Researchers also used rapamycin to treat these knockout mice - rapamycin can reduce the aging markers in immune cells and improve immune function. The results show that the aging phenotype of the knockout mice after treatment has improved significantly. This further confirmed the promoting effect of aging immune cells on systemic aging .
Transplantation of aged spleen cells into young mice will accelerate their aging
Finally, the corresponding author of the study of the study Laura Niedernhofer Professor said: "Now that we have determined which cell type is the most harmful, this work will guide us to develop an aging antidote for senescence . We also hope that it will help guide the discovery of biomarkers in the immune cell population, help determine who is at risk of tissue damage and rapid aging, and thus who needs aging treatment the most."
References :
1. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-658. doi:10.1111/acel.12344
2. Yousefzadeh, M.J., Flores, R.R., Zhu, Y. et al. An aged immuno system drives senescence and ageing of solid organs. Nature (2021). https://doi.org/10.1038/s41586-021-03547-7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-