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How long do proteins last in the body?
Proteins in the body can last from minutes to a lifetime. Human cell studies show half-lives from 18 minutes to months, while some lens and collagen proteins persist for decades.
Matic Broz Computational chemist
Proteins in the human body can last from less than an hour to an entire lifetime. Many measured proteins in the human proteome turn over in hours to days, but there is no meaningful average for every protein in the body.
The protein itself matters, and so do the cell, tissue, age, and measurement method. A regulatory protein that controls the cell cycle may disappear quickly. A structural protein in the eye lens or cartilage may remain for decades.
How long do proteins last in the body?
Body proteins last from minutes to a lifetime. In cultured human cells, median protein half-lives of several hours have been measured, while proteins in slowly renewing tissues can persist for years or for the life of the person.
One study of 803 newly synthesized proteins in human cells during DNA replication found a median half-life of 8.7 hours.[2] That is a useful cell-culture result, not a body-wide average. Experiments on different cells, tissues, and protein pools produce different distributions.
At the measured extremes, the mitochondrial lipid-transfer protein PRELID3B had a half-life of about 0.3 hours, or 18 minutes, in three human cell lines under blocked protein synthesis.[3] Radiocarbon dating found that crystallins in the central eye lens, formed around birth, undergo little or no subsequent turnover.[4]
These figures describe proteins made by the body. They do not describe how long dietary protein takes to digest or how long amino acids remain available after a meal.
What do protein half-life and turnover mean?
A protein's half-life is the time required for half of a measured protein pool to be removed. Protein turnover is the continuous replacement of old protein through degradation and new protein synthesis.[1]
Half-life describes a population of molecules, not the exact age at which each molecule disappears. It can include degradation, secretion, and dilution as cells divide. Stable-isotope labeling, pulse-chase experiments, radiocarbon dating, and translation-blocking assays also observe different parts of the process, so their results are not always directly comparable.
Sequence can affect stability, but sequence alone does not set a protein's lifespan. The instability index estimates whether a purified protein is likely to be stable from its amino-acid sequence. It cannot account for the cell's degradation machinery, the protein's binding partners, or tissue renewal.
Which proteins have the shortest and longest lifespans?
Short-lived proteins often regulate signaling, gene expression, and the cell cycle, while the longest-lived proteins tend to occur in structures with little capacity for replacement.
A 2021 study quantified 11,747 proteins across four human cell lines and classified 1,017 as short-lived, with half-lives of 8 hours or less. Roughly 100 measurements fell between 0 and 2 hours. PRELID3B was among the fastest at about 18 minutes, while the DNA-replication regulator Geminin lasted 3 to 4 hours.[3]
Eye-lens crystallins can remain for life because the mature cells in the lens nucleus cannot replace them.[4] Collagen also shows how strongly tissue changes the answer. A study based on amino-acid racemization estimated a half-life of 15 years for skin collagen and 117 years for articular-cartilage collagen.[5] Those estimates apply to collagen in those tissues, not to every collagen molecule in the body.
Proteins that persist for decades can accumulate chemical modifications because replacement is limited. This is one reason protein turnover matters to protein folding and proteostasis.
How does protein lifespan vary by tissue?
The same protein can have a half-life more than 150 times longer in one human cell type than another. Histone H1.2 lasted 18 hours in primary hepatocytes, 2,242 hours in B cells, and 2,741 hours in natural killer cells in the same study.[6]
The chart uses mean half-lives reported for primary, non-dividing human cells. Macro-H2A.1 ranged from 61 hours in hepatocytes to 1,950 hours in natural killer cells. Lamin B1 ranged from 388 to 3,215 hours.[6]
Whole tissues differ as well. In an isotope-labeling study of about 2,500 mouse proteins, average protein lifetime was 3.0 days in liver, 3.5 days in blood, and 9.0 days in brain.[7] These are mouse tissue averages, not human half-lives, but they show why a protein lifespan quoted without a tissue and measurement method is incomplete.
Sources▼
- Determining and interpreting protein lifetimes in mammalian tissues Trends in Biochemical Sciences · 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC9868050/
- Systematic study of the dynamics and half-lives of newly synthesized proteins in human cells Chemical Science · 2016. https://doi.org/10.1039/C5SC03826J
- Proteome-wide mapping of short-lived proteins in human cells Molecular Cell · 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8892350/
- Radiocarbon Dating of the Human Eye Lens Crystallines Reveal Proteins without Carbon Turnover throughout Life PLOS ONE · 2008. https://pmc.ncbi.nlm.nih.gov/articles/PMC2211393/
- Effect of collagen turnover on the accumulation of advanced glycation end products Journal of Biological Chemistry · 2000. https://pubmed.ncbi.nlm.nih.gov/10976109/
- Systematic analysis of protein turnover in primary cells Nature Communications · 2018. https://www.nature.com/articles/s41467-018-03106-1
- Analysis of proteome dynamics in the mouse brain Proceedings of the National Academy of Sciences · 2010. https://pmc.ncbi.nlm.nih.gov/articles/PMC2922600/
Founder and computational chemist, ProteinIQ
Dr. Matic Broz is the founder of ProteinIQ and a computational chemist. He completed a PhD focused on protein structure, molecular dynamics, and neural networks, and writes about structural biology and scientific software.