Recently The New York Times reported the following:
Can This New Enzyme Turn Back the Clock in the Human
Body?
In a recent study, scientists devised a way of reversing
the buildup of compounds that lead to some age-related diseases.
The NYT - By K. R. Callaway - K. R. Callaway is a science
reporter and a member of the 2026-27 Times Fellowship, a program for
journalists early in their careers.
July 24, 2026
The same chemical process that turns a baking cake golden
brown is at work aging your body’s cells. Over decades, your tissues, baking
steadily at 98.6 degrees, slowly accumulate compounds called advanced glycation
end products, or AGEs, as sugars interact with protein and fat in the
bloodstream. The buildup of AGEs is a hallmark of the aging process, making
tissues like collagen sticky and rigid and causing inflammation that can lead
to heart disease, eye damage, kidney disease and diabetes.
Researchers have tried unsuccessfully to develop medications that can stop AGEs from forming. But a new study, published on July 16 in the journal Nature Communications, describes a different tack: Scientists created an enzyme that cleans one of the most common AGEs from human tissue, helping to turn back the clock even after the aging compounds have settled in the body. This cleanse can help repair the tissue and has the potential to allow cells to act younger.
“It’s a small step in this bigger direction, because aging is very complicated,” said Aaron Cravens, a founder and the chief executive of Revel Pharmaceuticals, which developed the new enzyme, and the lead author of the study. “It’s the first time, I think, that anyone in the field has shown at the structural level that you can actually reverse some of these changes.”
Many efforts to develop treatments for aspects of aging have focused on cells, which gradually lose the ability to repair themselves and divide properly. Less attention has been given to the aging of longer-lived tissue structures such as collagen, which has a half-life of about 15 years.
Scientists have been aware of advanced glycation end products and their role in aging for decades. “It accumulates on tissue proteins like rust,” said John Baynes, a retired biochemist who was not involved in the study but who spent his career researching AGEs at the University of South Carolina Floyd School of Medicine.
But researchers have had “absolutely no success” trying to create drugs to inhibit the chemical reactions that produce AGEs, he said.
The new finding was “sort of a tour de force of modern biochemical and molecular biological techniques,” Dr. Baynes added. “To demonstrate that the darn thing worked on real proteins isolated from real tissue is really excellent work.”
The study by Dr. Cravens and his colleagues began with a hypothesis: Since all human tissue can be recycled into the biosphere after death, there must be a natural way to dissolve these compounds, even though they are extremely durable. To identify that process, they looked to the enzymes inside microbes, the agents of decomposition.
The team used artificial intelligence software to analyze the DNA sequences of more than 50,000 microbes and to compute the enzyme structures that each genetic code would create. They then narrowed the results to several candidates that seemed capable of cleaving AGEs from human tissue.
They eventually found one, and then engineered it to be more efficient at its task. After several cycles of guided evolution, the novel enzyme, called CMLase, became very good at removing AGEs from human tissue samples.
“In the most extreme case, we took 70-year-old human skin and brought the levels back to that of a 30-year-old,” Dr. Cravens said.
The researchers plan to start testing their enzyme for the treatment of eye diseases, including several associated with diabetes, that develop when AGEs accumulate in retinal and lens tissues. In theory, Dr. Cravens said, CMLase could be applied periodically or even just once to clear out the inflammatory buildup underlying these conditions.
“I was pretty excited about this paper,” said Michael C. Jewett, a bioengineer at Stanford University who was not involved in the study. “It’s not a clinical solution yet, but this proof of concept opens the aperture to possible new therapeutic solutions for longevity.”
If the approach works in a clinical setting, it has the potential to be applied to many AGE-related conditions, for example by improving the elasticity of collagen in skin or by restoring kidney or cardiovascular function.
“This study was a master class in how to engineer an enzyme,” Dr. Jewett said. “I think there is tremendous, untapped potential in this protein class for addressing numerous human diseases.”
Translation
這種新酶能讓人類身體時光倒流嗎？
在最近的一項研究中，科學家找到了一種方法，可以逆轉導致某些與年齡相關的疾病的化合物的累積。
使蛋糕變成金黃色的化學過程，同樣也在加速人體細胞的老化。幾十年來，人體組織在攝華 98.6 度的高溫下持續烘焙，隨著血液中的糖分與蛋白質和脂肪相互作用，會緩慢累積一種名為晚期糖化終產物（AGEs）的化合物。 AGEs 的累積是老化過程的標誌，它會使膠原蛋白等組織變得黏稠僵硬，並引發炎症，進而導致心臟病、眼部損傷、腎臟疾病和糖尿病。
研究人員曾多次嘗試開發能夠阻止晚期糖化終產物（AGEs）形成的藥物，但都以失敗告終。然而，7月16日發表在《自然通訊》雜誌上的一項新研究提出了一種不同的方法：科學家們研發出一種酶，能夠清除人體組織中最常見的AGEs之一，即使這些衰老化合物已在體內沉積，也能出現衰老進程逆轉。這種清除作用有助於修復組織，並有可能使細胞恢復年輕狀態。
研發出這種新型酶的Revel Pharmaceuticals公司創始人兼首席執行官、亦是該研究的主要作者Aaron Cravens表示，“這是朝著更大方向邁出的一小步，因為衰老是一個非常複雜的過程” ;“我認為，這是該領域首次有人在結構層面證明，我們確實可以逆轉其中一些變化。”
許多針對老化相關問題的治療方法都集中在細胞層面，因為細胞會逐漸喪失自我修復和正常分裂的能力。人們對膠原蛋白等壽命較長的組織結構的衰老關注較少，膠原蛋白的半衰期約為15年。
幾十年來，科學家一直關注著晚期糖化終產物（AGEs）及其在老化過程中的作用。John Baynes說:「它像鐵銹一樣在組織蛋白上積聚」。John Baynes是一位退休的生物化學家，他並未參與這項研究，但他在南卡羅來納大學佛洛伊德醫學院畢生致力於AGEs的研究。
但他表示，研究人員在嘗試研發抑制AGEs生成化學反應的藥物方面「完全沒有成功」。
Baynes博士補充說，這項新發現「堪稱現代生物化學和分子生物學技術的傑作」; 「這玩意能夠證明對從真實組織中分離出來的真實蛋白質是有效，這真是一項了不起的工作」。
Cravens博士及其同事的研究始於一個假設：既然所有人體組織在死後都可以循環利用到生物圈中，那麼即使這些化合物極其頑固，也必然存在一種自然的溶解方式。為了探明這個過程，研究人員將目光投向了微生物體內的酵素，它是一種分解劑。
研究團隊利用人工智能軟件分析了超過5萬種微生物的DNA序列，並計算出每種基因編碼所對應的酵素結構。隨後，他們將結果篩選至幾個似乎能夠從人體組織中裂解晚期糖化終產物（AGEs）的候選酵素。
最終，他們找到了一種酶，並對其進行改造，使其更有效率地完成這項任務。經過幾輪引導演化，這種名為CMLase的新型酵素能夠非常有效地從人體組織樣本中去除AGEs。
Cravens博士說: 「在最極端的情況下，我們提取了70歲老人的皮膚樣本，並將其AGEs含量恢復到了30歲老人的水平」。
研究人員計劃開始測試這種酵素在治療眼部疾病方面的應用，包括一些與糖尿病相關的眼部疾病，這些疾病的發生是由於AGEs在視網膜和晶狀體組織中累積所致。Cravens博士表示，理論上，CMLase可以定期使用，甚至只需一次，就能清除這些疾病背後的發炎累積。
並未參與這項研究的史丹佛大學生物工程師Michael C. Jewett說道: 「我對這篇論文感到非常興奮」; 「目前它還不是一個臨床解決方案，但這項概念驗證為延長壽命治療途徑帯來新曙光」。
如果這種方法在臨床環境中有效，它就有可能應用於許多與晚期糖化末期（AGE）相關的疾病，例如透過改善皮膚膠原蛋白的彈性，或恢復腎臟或心血管功能。
Jewett博士說: 「這項研究堪稱酵素工程的典範」; 「我認為這種蛋白質類別在治療多種人類疾病方面蘊藏著巨大的、尚未開發的潛力」。
So, in a new study scientists find an enzyme
that can clean up one of the most common AGEs from human tissue, helping us to
turn back the clock even after the aging compounds have settled in the body.
This cleanse can help repair the tissue and has the potential to allow cells to
act younger. Apparently, it’s a small step in this bigger direction, and there
is tremendous, untapped potential in this protein class for addressing numerous
human diseases.
Note:
1. Glycation
(non-enzymatic
glycosylation) (糖化) is the covalent attachment of a
sugar to a protein, lipid or nucleic acid molecule. Typical sugars that
participate in glycation are glucose, fructose, galactose, and their
derivatives. Glycation is the non-enzymatic process responsible for many (e.g.
micro and macrovascular) complications in diabetes mellitus and is implicated
in other diseases and in aging.
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