Core Insights - The research presents a comprehensive human proteome profile across a 50-year lifespan, revealing aging trajectories and signatures [2][3][21] - It identifies a significant aging turning point around the age of 50, with blood vessels being the earliest and most affected tissue [4][12][21] - The study highlights the decline in protein homeostasis as a core mechanism of aging, with implications for chronic inflammatory diseases and conditions like Alzheimer's [9][10][22] Group 1: Research Methodology - The study utilized ultra-sensitive mass spectrometry combined with machine learning algorithms to construct a proteomic aging map across seven physiological systems and 13 key tissues [3][21] - A total of 516 samples from 76 individuals aged 14-68 were collected, covering various organs such as the heart, aorta, lungs, and muscles [6][21] - The research identified 12,771 proteins, establishing organ-specific protein expression characteristics [7][21] Group 2: Key Findings on Aging - The research found that the correlation between mRNA and its translated proteins significantly decreases with age, particularly in the spleen, muscles, and lymph nodes [7][21] - Aging leads to a collapse of protein homeostasis, characterized by decreased synthesis capabilities, impaired folding and transport, and accumulation of amyloid proteins and immunoglobulins [9][21] - Blood vessels are identified as a "senohub," driving systemic aging processes through the expression of pro-aging proteins like GAS6 [14][15][21] Group 3: Implications for Anti-Aging Strategies - The study suggests potential anti-aging interventions targeting pro-aging proteins, such as developing CAR-T cell therapies against membrane proteins like GPNMB and neutralizing circulating proteins like GAS6 [18][21] - It emphasizes the importance of early intervention before the age of 50 to protect blood vessels and potentially delay systemic aging [18][21] - The findings provide a new paradigm for understanding systemic aging mechanisms through the lens of protein homeostasis imbalance and vascular aging [22]