Academy

Transcriptomic Aging Clocks

Transcriptomic aging clocks are computational tools that estimate a cell’s biological age based on its gene expression profile. Unlike traditional aging clocks that rely on DNA methylation patterns, transcriptomic clocks analyze the abundance of RNA transcripts in individual cells.

These clocks leverage single-cell RNA sequencing (scRNA-seq) data to capture the heterogeneity of aging processes within a tissue. Each cell’s transcriptome is input into a machine learning model, such as a neural network or regression algorithm, trained on samples from donors of known ages. The model learns which genes change expression consistently with aging and uses this information to predict the age of new cells.

Key Components:

• Training dataset: Thousands of single-cell transcriptomes from donors spanning a wide age range.
• Feature selection: Identification of genes whose expression strongly correlates with chronological age.
• Machine learning model: Algorithms such as elastic net regression or neural networks that map expression signatures to age predictions.

The AC3 Clock:

One example is the AC3 clock developed by Shift Bioscience. AC3 was trained on human dermal fibroblasts from donors aged 1 to 87 years. It achieves a Pearson correlation of over 0.9 at single-cell resolution without needing to aggregate cells or smooth data. AC3 enables high-throughput screens where each cell serves as an independent readout of age reversal.

Applications in Longevity Science:

1. Drug and genetic screens: AC3 can evaluate thousands of interventions simultaneously to uncover therapies that reduce cellular age.
2. Personalized medicine: Monitoring patient cell responses to anti-aging treatments in vitro.
3. Basic research: Studying the molecular hallmarks of aging at single-cell resolution across tissues.

Advantages:

• High throughput: Tens of thousands of cells can be profiled in one experiment.
• Single-cell resolution: Captures heterogeneity among cell types, identifying rare responses.
• Quantitative: Provides precise age estimates to measure partial rejuvenation.

Transcriptomic aging clocks are revolutionizing how researchers discover and validate anti-aging therapies by providing scalable, precise, and cell-specific measures of biological age.