{"id":1217,"date":"2024-05-27T21:10:23","date_gmt":"2024-05-27T21:10:23","guid":{"rendered":"https:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=1217"},"modified":"2024-05-27T21:10:23","modified_gmt":"2024-05-27T21:10:23","slug":"robust-rejuvenation-with-exosomes","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2024\/05\/27\/robust-rejuvenation-with-exosomes\/","title":{"rendered":"Robust Rejuvenation with Exosomes"},"content":{"rendered":"

A study out of Nanjing University last month brings exosome rejuvenation to the mainstream of researchers with broad new evidence and some speculations on mechanisms. The prominent publication in\u00a0Nature Aging<\/a>\u00a0corroborates and greatly expands results from Harold Katcher\u2019s Mumbai lab. Massive infusions of exosomes from young mice into old improve cognition, endurance, fertility, energy metabolism, heart function, immune function, bone density, cell senescence, and maximum lifespan.<\/em><\/p>\n

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History and context<\/span><\/div>\n<\/div>\n
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This current research grew from the Stanford lab of Tom Rando 20 years ago. An old mouse and a young mouse were sewed together so they shared a common blood supply. The old mouse showed signs of rejuvenation and the young mouse showed signs of accelerated aging.\u00a0Irina and Mike Conboy<\/a>\u00a0graduated and set up their own lab at Berkeley, where they demonstrated that it was not blood cells but something in the plasma that was responsible for the effect.<\/p>\n

Aging is not something that \u201chappens\u201d to cells. It is centrally orchestrated and information about age is transmitted through the bloodstream. Aging at the cell level responds to signals in the blood, even to the extent that old cells can become young in a \u201cyoung environment\u201d.<\/p>\n

The Conboys worked on removing old signaling from the blood. In cooperation with Dobri Kiprov, there is an\u00a0ongoing human trial<\/a>, simply removing blood plasma (but not the red or white blood cells) as a therapy.<\/p>\n

Twelve years ago,\u00a0James P Watson<\/a>\u00a0whispered to me, \u201cexosomes\u201d, but I was too distracted to listen.<\/p>\n

Seven years ago, Harold Katcher made an inspired guess and quietly conducted research in Mumbai, infusing rats with a blood plasma fraction he would only identify as \u201celixir\u201d or \u201cE5\u201d. In 2020, his team\u00a0announced<\/a>\u00a0that they had turned two-year-old rats to one-year-old rats according to the Horvath multi-species clock. I wrote about it as a \u201cbreakthrough<\/a>\u201d.<\/p>\n

From 2020-23, research proceeded slowly because Harold\u2019s business partner, Akshay Sanghavi, had trouble raising funds for industrial scale extraction of \u201cE5\u201d, and no one else knew what was in it.<\/p>\n

Then, last summer, a research group at Smidt Heart Inst in Los Angeles\u00a0announced<\/a>\u00a0promising results\u00a0rejuvenating rat hearts with exosomes<\/a>\u00a0from young rats. Akshay consented to reveal the secret that E5 was exosomes.<\/p>\n

What is an exosome? All cells release tiny information packages, wrapped in fats like a lipid nanoparticle. They contain DNA, RNA, proteins, as well as lipids, that communicate both within the body and through the air to other living things.<\/p><\/blockquote>\n

Would the phenotypic and epigenomic rejuvenation that Harold and Akshay observed lead to dramatically longer lifespans? We had data from only eight rats (all female), and results are not as consistent as we might hope. Median lifespan increased ~20%, depending what you use for a baseline, but curiously the maximum lifespan seems to be extended by 60% or more.<\/p>\n

The current paper adds lifespan data from only eight more rats (all male), but the range of metabolic and performance tests is greatly expanded.<\/p>\n

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Introduction<\/h2>\n
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I predict that\u00a0this new paper<\/a>\u00a0will bring exosome therapy into the mainstream. It begins inauspiciously.<\/p>\n

\u201cAging is an inevitable, time-dependent process that eventually limits the capacity of cells to maintain efficient homeostasis and repair mechanisms\u2026\u201d<\/p>\n

\u201cInevitable\u201d? If they really thought so, then they wouldn\u2019t be doing this research. My guess is that journal editors demanded this kind of language, both because I\u2019ve experienced such editor arrogance myself, and because Chinese researchers are less hypnotized by the\u00a0Selfish Gene ideology<\/a>\u00a0than biologists in the West.<\/p>\n

They continue, \u201cMechanistically, the aging process is predominantly attributed to the progressive accumulation of stochastic damages in cells, organelles and macromolecules.\u201d This is pure dogma. Despite this disclaimer, the method of their experiment is not to address stochastic damage in cells, but to adjust signaling in the organism as a whole.<\/p>\n

The fact that aging can be reversed with system-level signaling is a sign that it isn\u2019t just \u201centropy\u201d, that the body is in control, and, of course, that aging is not \u201ccell autonomous\u201d but centrally coordinated. Harold understands this, and it has been central to his key insights. But the mainstream theorists can\u2019t believe that natural selection would be so perverse, and they remain stuck in older paradigms. Perhaps these Chinese authors were compelled to make obeisance to old British dogmas as a price for being published in\u00a0Nature<\/em>. The paper was held up in peer review for an inexcusable 27 months.<\/p>\n

Results<\/h2>\n
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Old mice, starting in late middle age = 20 months, were given weekly intravenous infusions of exosomes from young mice for as long as they continued to live.<\/p>\n

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Median lifespan was increased 12%, and maximum lifespan increased 20%. This reminds us of Harold\u2019s exosome-treated rats, one of which lived much longer than the other seven. Usually we think that median lifespan is more malleable than maximum lifespan. For example, exercise increases median and mean lifespan, but not maximum lifespan. Here we find the opposite. More about this further down this column.<\/p>\n