画期的な研究で研究者らは、生物学的老化（寿命に比べて身体が老化するペース）は固定的ではなく、流動的であることを実証しました。 彼らは、異時性パラバイオシスマウスモデルを用いて、共有循環を通じて古い血液にさらされた若いマウスはより早く老化するが、古い循環が除去されるとこの影響は逆転することを示した。 彼らは、経験や環境への曝露によって時間の経過とともに蓄積するマーカーであるDNAメチル化時計を使用して、マウスの生物学的年齢を測定した。
研究者らは、マウスモデルとヒトストレスコホートを用いて、ストレス下では生物学的老化が加速するが、ストレス因子が除去されると減速することを実証した。 この老化の流動性は、精神的健康問題の潜在的な影響を含め、老化速度の引き金についての疑問を引き起こします。
人を若く見せると称する製品が市場に氾濫しています。 店頭にはアンチエイジングのクリームや美容液が並び、それだけでは不十分な場合は、ボトックスやフェイスリフト、脂肪吸引、クールスカルプティング、インプラントなどが常にあります。 しかし、老化を逆転させる鍵が…血液だったらどうなるでしょうか?
雑誌に掲載された研究では 細胞の代謝、ジェームズ・ホワイト博士、医学および細胞生物学の助教授。 ガープリート・バーツ博士、整形外科および病理学の助教授。 研究チームは、生物学的年齢（生涯の1年ごとに体が老化するペース）は流動的であり、ストレス下ではより早く老化する可能性がある一方で、それらのストレス因子が排除されれば元に戻る可能性があることを示した。
まず、研究チームは、若いマウスの血管が年老いたマウスに接続され、血液循環を共有する異時性並生マウスモデルを使用した。 古いマウスは接続すると老化のペースが遅くなりますが、若いマウスはより早く老化します。 「マウスを分離して古い血液循環を取り除くと、若いマウスは加速した老化を逆転させ、実年齢に戻ることができるのです」とホワイト氏は述べた。
マウスの生物学的年齢を決定するために、研究チームは次の方法を使用しました。[{” attribute=””>DNA methylation clocks. Experiences and environmental exposures leave little signatures on our DNA, and those signatures, or methylation marks, accumulate and can help scientists measure how fast or slow a person or animal is aging.
The team looked at the liver, heart, brain, kidney, and fat tissues of the mouse models two months after completing parabiosis, and using a variety of DNA methylation clocks, determined that all young mice aged faster when exposed to old blood and reversed back to baseline age after separation and recovery.
“We show evidence for a reversal of biological aging,” White said. “The young mice, which showed accelerated biological age with exposure from aged circulation, were able to reverse this process and return back to their chronological age after the old circulation was gone.”
Obviously, it’s not exactly natural to be surgically attached via blood vessels to another living creature, so the team wondered whether the same fluctuation in biological aging could be true without sharing old blood.
In collaboration with Harvard University, they analyzed human cohorts of stress that included chronic illness, surgery, and pregnancy. Using DNA methylation clocks on blood samples, they found that aging can accelerate during these stressful events, but when the stressors are removed, aging can decelerate.
“This is the first time in in vivo human cohorts that we were able show the pace of aging isn’t just Father Time,” White said. “It accelerates, and hopefully, decelerates over time.”
This held true for patients needing emergency surgical repair for a traumatic hip fracture. Blood samples were taken before surgery, one day after surgery, and before patients were discharged from the hospital. The team found a significant increase in biological age markers in the first 24 hours of hospital admittance, but by the time they were discharged, patients’ biological ages dropped, even though many of these patients were in their 70s and 80s.
Interestingly, the same was not true for patients who elected to have hip replacement surgery. Without the trauma of an injury, biological aging was not affected.
COVID-19 patients who ended up in the intensive care unit also aged more rapidly during their illness. It’s important to note that blood samples were not taken from these patients prior to their admittance to the ICU, so the team used DNA methylation clocks to analyze their biological age while in the ICU and compared that to their biological age after they recovered. “We saw varying results but generally trending back to recovery,” White said.
This begs the question: Is there a point of no return? In other words, can a person’s pace of aging increase so much because of an acute injury; lifestyle choice, such as smoking or drinking; or maybe even mental health trauma that they can’t fully “go back in time” and reverse it?
The short answer: we don’t know yet.
“Our next steps,” White said, “are to figure out the triggers of why different responses drive acceleration or deceleration of aging.” White wants to explore whether it’s only physical injury or illness and recovery that can accelerate and decelerate aging, or whether other factors, such as depression and mental illness, can also accelerate aging. And if so, can aging decelerate if those mental health issues are resolved?
“I think the tissues and cells respond to their environment,” White said. “So, in theory, if we can convince the cells they are young and take out stressors, maybe we can push off aging a while longer.”
For more on this research:
Reference: “Biological age is increased by stress and restored upon recovery” by Jesse R. Poganik, Bohan Zhang, Gurpreet S. Baht, Alexander Tyshkovskiy, Amy Deik, Csaba Kerepesi, Sun Hee Yim, Ake T. Lu, Amin Haghani, Tong Gong, Anna M. Hedman, Ellika Andolf, Göran Pershagen, Catarina Almqvist, Clary B. Clish, Steve Horvath, James P. White and Vadim N. Gladyshev, 21 April 2023, Cell Metabolism.
DOI: 10.1016/j.cmet.2023.03.015