As the body ages, organ function deteriorates and the risk of age-related diseases such as cardiovascular, cancerous and neurodegenerative. A better understanding of this decline could serve to promote healthier old age.
Now, a scientific team from the Baylor College of Medicine, the Chan Zuckerberg Biohub in San Francisco, and the company Genentech (all US) published in Science he first atlas of fruit fly cellular aging (Drosophila melanogaster), which characterizes in detail the aging process in 163 different cell types of this insect.
He Atlas of aged fly cells (AFCA), which will have open access to researchers, revealed that the different types of cells in the body age differently, each of them following a process that involves specific patterns.
As explained to SINC, co-author of the study, hongjie li, Baylor Professor of Molecular Genetics, his team “characterized the 163 cell types with a high degree of reliability at four different ages of the fly’s life. As far as we know, it’s the most complete data set It covers most major cell types throughout the aging body.
Fat cells: nuclear cleavage without replication
“We found that fat or adipose cells significantly increase their nuclear number during aging. our data live show that the increase is due to an atypical event, in which these cells undergo nuclear cleavage without DNA replication. As far as we know —he emphasizes— this is the first time that this phenomenon has been reported”.
In this sense, the team found that “the cell types that age faster are the adipose cells and those of the liver, which constitute the main tissues that control metabolism. It’s possible the same thing could happen to humans, Li says. “Yes we can slow down the aging of these types of cellswe can obtain the maximum health benefit”.
We have developed aging clock models for 64 cell types and demonstrated which cell types and genes can be used to best predict biological age.
In addition, the authors observed that aging affects the cellular composition of all flies “We developed aging clock models for 64 cell types and showed which cell types and which genes can be used to better predict biological age”, says the expert.
To do this, they analyzed various biological characteristics of individual cell types as fruit flies aged naturally in the laboratory. According to the researcher, “this is a widely used animal model, as 75% of the genes associated with human diseases have functionally similar counterparts in this type of fly”.
Analysis of changes in gene expression
As the dipterans aged, the scientists collected samples that were 30, 50 and 70 days old (the latter is equivalent to an 80-year-old person). At each moment, one single core RNA sequencing analyze changes in gene expression in individual cells from different organs and compare the results with those of young flies (5 days old).
The team examined four distinct characteristics of aging: changes in cellular composition, number of differentially expressed genes, variation in their number and decrease in cellular identity. The authors observed that, as flies age, these characteristics change together in specific patterns for each cell type.
Another of the relevant discoveries, says Li, “is that we observed a divergence in the contribution of different cell types to the aging phenotype of a tissue. For example, in the female reproductive system drosophila, follicular cells aged very quickly, while germ cells aged slowly. This indicates that the age-related decline in female fertility is likely primarily influenced by aging follicular cells.”
The authors also found that about 80% of all cell types tested decreased the number of expressed genes and 20% increased it. “We plan to study the mechanism of this observation in the future,” he says. Tzu Chiao Luanother of the co-authors and researcher at Baylor.
Furthermore, they investigated whether the cellular gene expression processes that define cellular identity change as animals age. For example, according to the expert, “compared to the Nig1 flight muscle identity marker in young flies, this marker dramatically decreases in older flies, while others began to appear as the flies aged.”
“We learned that each of the four characteristics of aging we studied measured a different aspect of the cell and that no single characteristic applies to all cell types”, emphasizes Li.
unique aging patterns
Combining all the characteristics of aging, he adds, “led us to discover unique aging patterns specific to each cell type, and comparing these led to useful and interesting discoveries. For example, they saw that “neurons in the brain age slowly, while muscle, fat and liver cells do it much faster. Furthermore, these standards may vary by gender.”
for your part, heinrich jasperstudy co-author and researcher at Genentech, emphasizes that “a key observation of this study is that these unique standards can be used to calibrate biological age, that is, the relative aging state of an organism, regardless of its chronological age . “
These specific standards can be used to calibrate biological age, i.e. the relative aging state of an organism, independent of its chronological age.
In Jasper’s opinion, “this will allow us to better understand factors such as diet, medications and diseases that can alter the trajectory of aging and thus make an organism ‘younger’ or ‘older’ than its chronological age”.
A tool to investigate aging
For Stephen QuakeProfessor of Bioengineering at Stanford University and co-author of the paper, the new atlas is a powerful open access resource for scientists to better understand the biology of aging.
“Through a very productive collaboration, our team has created an exceptionally detailed map of how gene expression changes with aging across a wide range of cell types in the fly.”
According to Quake, “Since most of these genes have similar functions in people, this dataset offers a unique vantage point to begin to unravel why many serious human diseases arise later in life.”
Hongjie Li also explains that in this study they applied their aging clock models to the Atlas of the Aging Rat (Nature2020) that identifies predictive genes for aging in this animal.
Since most of these genes have similar functions in people, this dataset offers a unique insight into why many serious human diseases arise later in life.
“We compared the aging genes of the fly and the mouse and found that changes in the expression of the ribosomal protein gene are conserved predictors in both models”, he points out.
Finally, this expert points out that Atlas of aged fly cells constitutes a valuable tool and will be of interest to the research community: “It has the potential to serve as a benchmark for whole-organism aging and could be used as a basis for exploring how different changes increase lifespan at a cellular scale.”
O Drosophila melanogaster It was also the ‘protagonist’ of another scientific milestone in March, when two teams from the United States and the United Kingdom published the first complete map of the insect’s brain and its neural connections.
Reference:
“Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution.” Science (June 2023).