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Mapping the Mechanisms of Aging
Aging is a universal experience, evident through changes like wrinkles and graying hair. However, aging goes beyond the surface; it begins within our cells. Over time, our cells gradually lose their ability to perform essential functions, leading to a decline that affects every part of our bodies, from our cognitive abilities to our immune health.
To understand how cellular changes lead to age-related disorders, Calico scientists are using advanced RNA sequencing to map molecular changes in individual cells over time in the roundworm, C. elegans. Much like mapping networks of roads and landscapes, we’re charting the complexities of our biology. These atlases uncover cell characteristics, functions, and interactions, providing deeper insights into how our bodies age.
In the early 1990s, Cynthia Kenyon, Vice President of Aging Research at Calico, and her former team at UCSF discovered genes in C. elegans that control lifespan; these genes, which influence IGF1 signaling, function similarly to extend lifespan in many other organisms, including mammals. The genetic similarities between this tiny worm and more complex animals make it a useful model for studying the aging process. In work published in Cell Reports last year, our researchers created a detailed map of gene activity in every cell of the body of C. elegans throughout its development, providing a comprehensive blueprint of its cellular diversity and functions. They found that aging is an organized process, not merely random deterioration. Each cell type follows its own aging path, with many activating cell-specific protective gene expression pathways, and with some cell types aging faster than others. Even within the same cell type, the rate of aging can vary. Interestingly, in older worms, certain genes that extend lifespan become more active, showing that their bodies actively respond to growing old. 
And this isn’t unique to worms, the specific characteristics of cells significantly impact how mice age, influencing both the course and extent of their aging process; we reported on this in Genome Research. “It’s fascinating to make connections between the cellular pathways that change with age across huge evolutionary distances,” says David Kelley, Principal Investigator at Calico. “This suggests there are fundamental challenges and tradeoffs that all organisms face. Understanding them better will hopefully point us to ways to alleviate them and slow aging.” Our discoveries offer a glimpse into the cellular mechanics of aging, providing a valuable resource for studying these biological processes in other organisms, including humans.
Mapping Aging Mechanisms for Future Interventions 
As our population grows old, more people are facing age-related ailments such as Alzheimer’s, heart disease, arthritis, and cancers. Our atlases give us a unique window into understanding how different cell types interact as tissues age. Studying this cellular “crosstalk” reveals insights into how shifts in cell communication drive disease progression, opening up new possibilities for improving health outcomes as we age. 
Read the full stories, Individual cell types in C. elegans age differently and activate distinct cell-protective responses in Cell Reports and Murine single-cell RNA-seq reveals cell-identity-and tissue-specific trajectories of aging in Genome Research. 
Our interactive C.elegans and Murine cell atlases are publicly available.
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