The Aging of Macrophages Impairs Peripheral Nerve Regeneration

Macrophages of the innate immune system, cells derived from monocytes, are involved in many processes in tissue beyond merely hunting down invading pathogens. They are also important to the processes of tissue maintenance regeneration following injury. Like all aspects of the immune system, macrophage behavior becomes dysregulated with age, a consequence of changes in the signaling environment that result from the accumulation of molecular damage that causes aging. Here, researchers demonstrate that this aging of the immune system degrades the ability of the peripheral nervous system to regenerate, and that exposing macrophages to a more youthful tissue environment reverses some of this lost regenerative capacity. Further, they identify a little of the regulatory biochemistry involved in this aspect of degenerative aging.

The regenerative capacity of injured peripheral nerves is diminished with aging. To identify factors that contribute to this impairment, we compared the immune cell response in young versus aged animals following nerve injury. First, we confirmed that macrophage accumulation is delayed in aged injured nerves which is due to defects in monocyte migration as a result of defects in site-specific recruitment signals in the aged nerve. Interestingly, impairment in both macrophage accumulation and functional recovery could be overcome by transplanting bone marrow from aged animals into young mice. That is, upon exposure to a youthful environment, monocytes/macrophages originating from the aged bone marrow behaved similarly to young cells.

Transcriptional profiling of aged macrophages following nerve injury revealed that both pro- and anti-inflammatory genes were largely downregulated in aged compared to young macrophages. One ligand of particular interest was macrophage-associated secreted protein (MCP1), which exhibited a potent role in regulating aged axonal regrowth in vitro. Given that macrophage-derived MCP1 is significantly diminished in the aged injured nerve, our data suggest that age-associated defects in MCP1 signaling could contribute to the regenerative deficits that occur in the aged nervous system.

Link: https://doi.org/10.3389/fnagi.2020.00174

Comments

$4.36MM in expenses

$2.68MM in revenues

Remind me again why anyone would give a penny to this organization as opposed to seeding a promising new company where 100% of the money can go to R&D, and not all this "outreach / education"?

Posted by: devon mcradle at September 16th, 2020 11:21 AM

There would not be such new companies without outreach/education.

Posted by: Antonio at September 16th, 2020 12:08 PM

@Antonio

Nonsense

There are thousands of biotech companies around the world, and many being seeded on a daily basis

They don't need cheerleaders to generate interest, sucking away valuable R&D $$$ / resources

Posted by: devon mcradle at September 16th, 2020 12:23 PM

@Devon:
Nonsense.
There have been no biotech companies dedicated to SENS research until the last 5 years or so, nevertheless SENS is 20 years old. Many of the founders of SENS-related biotechs (Ichor, Underdog) where SRF students, or knew about SENS in a SENS conference and repurposed their R&D to SENS problems (Covalent), or were SRF funders (Oisin). Arigos is another biotech founded by a SENS student, albeith not dedicated to SENS research but cryonics research.

Posted by: Antonio at September 16th, 2020 1:14 PM

The world doesn't end at SENS.
It's good that other promising approaches like epigenetic reprogramming, to name one, and translational efforts get cash too.

Posted by: Barbara T. at September 16th, 2020 1:56 PM

@Antonio

If all those projects were of any real value to the biotech industry, they would not need SENS cheerleading - just R&D money

Sorry - 100% of $$ should go to R&D of real projects - not to advocacy - with the exception of rare diseases

Posted by: devon mcradle at September 16th, 2020 2:38 PM

It's my fault thinking I was discussing with an adult. Bye.

Posted by: Antonio at September 17th, 2020 1:24 AM

Antonio, just state what you believe and leave it at that. Some people will never change their thoughts for some crazy reason. I'm very thankful for SENS and also for Reasons blog. Two examples of selfish less people/ groups.

Posted by: Robert at September 17th, 2020 2:18 AM

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