Aging Unfolds in Distinct Stages Across the Body
A landmark study by Rockefeller University has revealed new perspectives on aging, showing that it occurs in distinct stages marked by synchronized cellular changes across organs. Published in Science, the research provides a transformative view of aging, showing it is not a gradual decline but a developmental process triggered by molecular cues. Junyue Cao and his team utilized single-cell sequencing to analyze over 21 million cells from five life stages of mice, creating the largest cellular atlas of mammalian aging to date.
The findings highlight that certain cell populations expand or diminish at specific times across multiple organs. These shifts, driven by shared molecular features, suggest potential targets for delaying or reprogramming aging. “Some cells greatly expand in number while others decline, depending on the age,” said Cao. “What’s more, some changes are controlled by the same molecular features, which could help us intervene in the aging process itself.”
Technological Breakthroughs: The Universal Platform
To achieve this groundbreaking research, the team adapted EasySci, a single-cell sequencing method initially developed to study brain aging. Graduate student Zehao Zhang modified the protocol to profile cells across all major organs, tackling the challenge of maintaining data quality across diverse tissues.
This effort resulted in a universal profiling platform capable of systematically analyzing aging and disease mechanisms across an entire organism. Using EasySci, the team collected and analyzed data from over 600 samples of male and female mice. This approach enabled them to identify over 10 main cell types and 200 subtypes with significant age-related changes.
For example, early adulthood in mice (3 to 12 months) saw a decline in specific fat, muscle, and epithelial cells, while advanced adulthood (12 to 23 months) exhibited a surge in immune cells. Intriguingly, these changes were linked to gene expressions shared across different organs, offering insights into perspectives on aging and how these processes might be regulated.
Insights into Sex Differences and Future Applications
One of the study’s most surprising findings was the profound cellular differences between male and female mice. Hundreds of cellular states varied by sex, including adipocyte progenitor cells and aging-associated B cells, which expanded in females. These differences may explain the higher prevalence of autoimmune conditions in older women compared to men. Zhang emphasized the importance of including both sexes in aging studies to uncover generalized mechanisms and develop sex-specific treatments.
The research has also laid the groundwork for future studies. The dataset, named PanSci, is the largest single-cell sequencing atlas of mammalian aging ever created. Researchers worldwide are encouraged to explore this resource to advance understanding in fields like age prediction, rare cell identification, and disease mechanisms.
Cao’s team plans to further investigate the cellular dynamics linked to aging and sex differences, focusing on underexplored subtypes. “Our findings could help identify the cellular basis for some sex-specific diseases,” said Cao. The comprehensive dataset also offers opportunities to train machine-learning models, enabling in silico experiments and other computational applications.
This study marks a significant step in unraveling the complexities of aging, offering insights that could shape interventions for age-related conditions and improve perspectives on aging in the human process.
