Aging has traditionally been viewed as a gradual process, closely tied to the passage of time. As individuals age, they may notice a slight decrease in energy levels and the appearance of wrinkles. However, a significant new study suggests that aging is not a linear experience. Instead, it accelerates dramatically around the age of 50, with various organs experiencing decline at distinctly different rates. This comprehensive research presents the most detailed understanding of how human tissues age, based on extensive analysis of tens of thousands of proteins extracted from actual human organs.
The study reveals that aging is not uniform across the body but occurs in distinct phases marked by molecular upheaval. According to the authors, “Temporal analysis revealed an aging inflection around age 50, with blood vessels being a tissue that ages early and is markedly susceptible to aging.” This finding underscores the complexity of the aging process and its varying impact on different biological systems.
Led by researcher Guang-Hui Liu at the Chinese Academy of Sciences, the team created a “proteomic atlas” of human aging. They collected tissue samples from 76 individuals aged between 14 and 68, all of whom had died from accidental brain injuries. These samples encompassed 13 different tissues from major biological systems, including cardiovascular, digestive, immune, and endocrine systems. Utilizing mass spectrometry, the researchers profiled over 12,700 unique proteins from each sample, providing valuable insights into how protein levels fluctuate with age.
Rather than observing a smooth decline, the researchers identified an inflection point, particularly between the ages of 45 and 55, during which protein expression changed dramatically across various organs. Notably, the aorta, the body’s main artery, aged the fastest and most significantly among all tissues assessed.
One of the most intriguing revelations from the study is that the aorta may not only age prematurely but could also accelerate aging in other parts of the body. The researchers found specific proteins in the aged aorta that appear to promote damage in other tissues. A protein named GAS6 emerged as particularly noteworthy. When injected into young mice, it led to rapid signs of premature aging, including decreased grip strength, poor balance, and visible vascular damage. The authors suggest, “These insights may facilitate the development of targeted interventions for aging and age-related diseases.” This supports the theory that aging is a systemic and coordinated process, with blood vessels acting as a “senohub”—a central relay station for distributing molecular signals of decline.
To monitor how different organs age, the researchers developed organ-specific “proteomic clocks.” These algorithms can predict a tissue’s biological age based on protein levels. The findings indicate that organs do not age uniformly; for instance, the adrenal gland begins to exhibit changes in the 30s, while the spleen and pancreas show significant shifts after age 50. Alarmingly, as individuals age, there is a noted breakdown in the synchronization of protein production and mRNA expression, particularly in older tissues.
A further finding revealed signs of “proteostasis failure,” a breakdown of the systems that ensure proteins remain correctly folded and functional. This failure is characterized by the accumulation of amyloid proteins, known for their association with diseases like Alzheimer’s. In this study, amyloid proteins were not only found in the brain but across various organs, suggesting a broader implication for aging. The authors state, “The amyloid-immunoglobulin-complement axis may constitute a crucial component of the aging tissue microenvironment.” This molecular cascade—characterized by protein misfolding, inflammation, and immune activation—has led to the concept of “inflammaging.”
The notion that aging occurs in waves is not new, with prior studies indicating inflection points around ages 44 and 60, and even a significant shift at age 80. This latest research reinforces the idea that aging unfolds in phases rather than in a linear fashion. The strength of this study lies in its use of solid tissue samples, providing more precise information compared to earlier studies that primarily relied on blood biomarkers. However, it does have limitations, such as excluding critical organs like the brain and kidneys, which may affect the study's generalizability.
Despite its limitations, the data presented in this study is among the most robust to date. The researchers suggest that understanding the timing and nature of organ decline could lead to tailored interventions. They propose that plasma proteins, many of which correlate with their tissue of origin, could one day serve as non-invasive biomarkers for tracking organ-specific aging. Additionally, some proteins, such as GPNMB and NOTCH3, which increase with age in both tissues and blood, have shown potential for accelerating aging in mice and human cells when artificially introduced. These proteins could become targets for future therapies, including vaccines or drugs designed to selectively eliminate senescent cells.
In conclusion, this groundbreaking study highlights the early and pronounced aging of the aorta, emphasizing the significant role of vascular senescence in initiating systemic aging. While we cannot stop time, understanding which organs age first may provide crucial insights into aging and age-related diseases. As research continues to evolve, we may soon have more refined strategies for monitoring and potentially mitigating the effects of aging.
