Scientists have discovered molecular markers for ovarian aging

, published online in the journal Cell, researchers used high-precision single-cell transcription group sequencing techniques to map for the first time the aging of the ovaries of crab-eating monkeys. Using a joint analysis of this map and the human ovarian cell research system, the researchers found that the decline in antioxidant capacity associated with aging is one of the main characteristics of primate ovary aging.
the study was carried out by researchers Liu Guanghui, Qu Jing, Professor Tang Fuhui of Peking University and the Salk Institute of the United States.ovary structure is complex and the cellular composition is highly heterogeneic, consisting of several follicles at different stages of development, as well as a variety of other cell types that provide the necessary nutrients and support for follicle development. "It's like a sophisticated mechanical clock with a variety of gears of different sizes and uses connected and working together to make sure it works properly." Wang Si, one of the study's
the Institute of Animals and Animals, said.
, it is difficult to accurately reveal the aging law and molecular regulation mechanism of different types of cells in the aging process by using traditional research techniques.
addition, due to ethical and sample source constraints, it is difficult to obtain normal ovarian tissue across young and old humans. To some extent, this limits people's understanding of the mechanism of human ovarian aging, but also restricts the development of female ovarian aging and related disease interventions.non-human primates are highly similar to humans in terms of the basic characteristics of the ovaries and aging characteristics. The researchers obtained the ovarian tissue of young and old crab-eating monkeys, and through histological pathological analysis, they found that the number of latched follicles in the ovary tissue of elderly crab-eating monkeys increased, the number of healthy follicles decreased, and the degree of fibrosis increased. These characteristics indicate delintic changes in structure and function in the ovaries of older non-human primates.
Through high-precision single-cell transcription group sequencing techniques, the researchers systematically revealed the gene expression characteristics of primate major cell types such as ovaries, granulocytes, substituts, smooth muscle cells, endotrine cells, natural killer T-cells and macrophages, and identified and verified new marker genes specific to multiple ovarian cells.
Because the follicle development process consists of multiple stages and is more complex, "based on the stage-specific molecular expression level and transcription factor regulation network, we analyzed four sub-groups of ovaries at different stages of developmental changes in single-cell resolution, and found important transcription factors and their co-regulation mechanisms for regulating these sub-groups." Wang Si said.
further exploration, it has been found that aging leads to redox control network imbalances in different types of cells in the ovaries. During aging, mitochondrial function of early ovarian cells is impaired, and the expression of oxidase-related genes (e.g. GPX1, GSR, etc.) is significantly reduced. These results suggest that early ovarian cells are more sensitive to aging-related oxidative stress than ovaries in the middle and late stages.
addition, granulocytes, as "caregivers" of ovary cells, play an important role in nutrition and support during follicle development and maturation. The study found that the oxidative damage of granulocytes increased during aging, accompanied by an increase in apoptosis gene expression and a reduction in gene expression associated with redoxase.
basis, we identified redox regulatory genes such as IDH1 and PRDX4 as new molecular markers of granulocyte aging. Wang Si said., do human ovaries have cellular molecular events similar to those of crab-eating monkeys during aging?
to answer this question, researchers isolated granulocytes from follicle fluid in healthy women who were treated with assisted reproductive technology. Using these cells, the increase of oxidative damage of the aforementioned aging-related cells and the expression changes of the new aging markers were verified. At the same time, a causal link between redox gene expression changes and apoptosis and mitochondrial dysfunction was confirmed in human particle cells.
study is the first published internationally available, high-precision single-cell transcriptional spectrometry study of aging of non-human primate organs. The unstable molecular mechanism of cell type-specific redox regulation is revealed, and it is proved that this is a common feature of ovarian aging in primates, including humans.
" Our study deepens people's understanding of ovarian structure and function as they age, analyzes the susceptibility and specific susceptibility of different types of ovarian cells during aging, and provides information on potential regulatory targets for ovarian aging, including in people. Zhang Weixuan, co-lead author of the study
The Beijing Institute of Genomics, said.
"This provides a new biological marker for the detection and early warning of ovarian aging and decreased fertility in women, and provides a theoretical basis for interventions in ovarian aging-related diseases," she said. For
paper information: