Ageing—a universal yet complex biological process—affects every aspect of our bodies. While ageing remains inevitable, understanding its intricacies may pave the way for healthier and longer lives. Recent research introduces an innovative approach using “tissue clocks” to predict biological ageing and reveal how different organs age at varying rates. This blog will delve into these findings and explain their potential to revolutionize ageing research and healthcare.
What Are Tissue Clocks?
Tissue clocks are deep learning-based models that estimate biological age using histopathological images. These images capture the microscopic structure of tissues, offering a glimpse into the wear and tear our organs undergo with time. Unlike chronological age—the number of years we’ve lived—biological age reflects how old our tissues and organs really are.
By analyzing over 25,700 tissue images from 983 individuals across 40 tissue types, scientists created these clocks to predict biological age with remarkable accuracy. The average error in these predictions was just 4.9 years, underscoring the power of combining advanced imaging and artificial intelligence.
Study Behind the Breakthrough
Researchers from University of Vienna utilized data from the Genotype-Tissue Expression (GTEx) project, a comprehensive resource that provides tissue samples and genetic data. The individuals in this study ranged from 20 to 70 years old, with tissue samples collected from diverse organs such as the brain, heart, lungs, and skin.
Using advanced AI models, the researchers quantified morphological changes in tissues and trained their models to correlate these changes with age. These “tissue clocks” not only measured biological age but also identified disparities between chronological and biological age, referred to as “age gaps.” Such gaps could indicate accelerated ageing or resilience in specific tissues.
Key Findings
1. Ageing Patterns Vary Across Tissues
The study revealed that tissues age at different rates. Some organs, like the lungs and glands, show accelerated ageing as early as 20 to 40 years old. Others, such as the colon and aorta, experience ageing in distinct phases, with peaks occurring later in life.
Interestingly, the uterus exhibited a unique ageing trajectory, with the fastest changes coinciding with menopause. This highlights how hormonal shifts can significantly impact ageing.
2. Age Gaps Reflect Health and Disease
Age gaps—the difference between biological and chronological age—offer valuable insights into health. Larger age gaps were linked to shorter telomeres, which are protective caps on chromosomes that shorten as we age. Tissues with greater age gaps also displayed more subclinical pathologies and higher comorbidity rates.
For instance, individuals with heart disease showed accelerated ageing in adipose tissue, while those with diabetes exhibited faster ageing in the pancreas. These findings suggest that tissue clocks could help identify early signs of age-related diseases.
A Closer Look at Tissue-Specific Ageing
1. Morphological Changes
The research highlighted specific structural changes in tissues as they age. Common patterns included:
Atrophy: A reduction in tissue size and function, observed across various organs.
Fibrosis: Increased scarring, which hampers normal tissue function.
Microvascular Rarefaction: A decrease in tiny blood vessels, limiting oxygen and nutrient delivery.
These changes reflect the cumulative damage tissues endure over time, underscoring the importance of maintaining cellular health.
2. Molecular Insights
By integrating tissue clocks with gene expression data, researchers identified genes associated with ageing. For example, the EYA4 gene—linked to hearing loss—was upregulated in ageing adipose tissue. Similarly, IGFBP2, a gene promoting oncogenic processes, increased with age in adrenal glands.
These molecular markers could serve as potential targets for therapies aimed at slowing or reversing ageing.
Blood as a Window into Ageing
The invasive nature of tissue sampling poses challenges for widespread application. To address this, researchers developed a method to predict tissue-specific age gaps using blood samples. By analyzing gene expression in blood, they identified systemic ageing signals that reflected the health of multiple tissues.
This approach was validated in external cohorts, including individuals with Crohn’s disease and rheumatoid arthritis. Patients with these conditions exhibited greater age gaps in specific tissues, emphasizing the utility of blood-based predictions for disease monitoring.
Applications and Implications
1. Early Detection of Age-Related Diseases
Tissue clocks could help identify individuals at risk of conditions like cardiovascular disease, diabetes, and neurodegeneration. By detecting accelerated ageing in specific organs, doctors could intervene earlier, improving outcomes.
2. Personalized Medicine
Understanding how different tissues age could enable tailored therapies. For instance, interventions targeting fibrosis could slow ageing in organs prone to scarring, such as the lungs and liver.
3. Non-Invasive Monitoring
Blood-based age predictions offer a non-invasive way to monitor ageing. This could lead to routine tests that track biological age and guide lifestyle or medical interventions.
4. Insights into Healthy Ageing
By studying resilient individuals—those with lower biological ages than their chronological age—scientists could uncover factors that promote longevity and healthspan.
Challenges and Future Directions
While promising, this research faces several limitations:
Data Imbalance: The GTEx dataset included more male than female samples, potentially affecting the accuracy of tissue clocks for female-specific organs.
Postmortem Samples: Using tissues from deceased individuals introduces variability due to autolysis, which researchers attempted to mitigate.
Causality vs. Correlation: The study identified associations but couldn’t establish causality. Future research combining genetic and environmental data could address this gap.
Invasiveness: Despite the potential of blood-based predictions, some applications still require tissue biopsies, limiting their feasibility for routine use.
A Vision for the Future
The development of tissue clocks marks a significant step forward in ageing research. By combining histological analysis, molecular data, and AI, scientists are uncovering the intricate interplay between cellular, tissue, and systemic ageing.
In the future, these tools could transform healthcare by enabling:
Routine ageing Assessments: Blood tests that provide a comprehensive picture of biological ageing.
Targeted Therapies: Interventions tailored to slow ageing in specific tissues.
Healthspan Extension: Strategies to delay the onset of age-related diseases and improve quality of life.
Conclusion
Ageing is a multifaceted process influenced by genetics, environment, and lifestyle. Tissue clocks provide a novel lens to study this complexity, revealing how different organs age and highlighting potential interventions. As research progresses, these insights could pave the way for a future where age truly becomes just a number.
The study is published in the journal BioRxiv. It was led by Ernesto Abila.
