"Nature" is heavy: young immune cells can reverse aging!

Open today's "Nature" update, the singularity cake can't help but think secretly, exchange blood to resist aging, it is impossible to say.
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This research comes from the research team of the University of Minnesota[1], the researchers found that the aging of immune cells is unexpected Not only will it lead to impaired immune function, it will also promote the damage of other non-immune organs and cause mice to short-lived.

Transplanting senescent immune cells can also promote aging and tissue damage; conversely, transplanting "young" immune cells can reverse aging to a certain extent.

So.
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who has young and strong immune cells, share it! Source | Why does the study of aging on pixabay study the head of immune cells? In recent years, scientists have actually realized that since aging is the main risk factor for most chronic diseases, aging itself may actually become a target of treatment.

To treat senescence, the actual operation must fall on senescent cells.

Senescent cells are a type of cells in a special state that basically stop proliferating, but still retain their metabolic activity.
A major feature is the senescence-related secretory phenotype (SASP) that mainly secretes inflammatory cytokines, growth factors, and proteases.

A small amount of senescent cells can lead to the decline of body functions.

At present, scientists have developed a series of drugs targeted to eliminate senescent cells.
These drugs are called senolytics, and they have also shown certain effects in preclinical studies.

But there are some problems with this idea.

We can't get rid of all senescent cells in a single brain.
Not only can a single drug not achieve such a comprehensive removal [2], even if it can be done, it may not be safe.

Then there is a new solution-which kind of senescent cells has the greatest effect on aging, let's fight it first! From this, researchers thought of immunity.

With the aging of the body, immunity is also aging, which limits the resistance to pathogens and cancer cells, which is why the elderly are more likely to get sick and less sensitive to vaccines [3].

If the problem of immune aging can be solved first, it should be very helpful to defeat the overall aging.

Here, the researchers used a method of specifically knocking out ERCC-1 to make mice immune "decay before old age.
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ERCC-1 is a key enzyme for DNA repair.
Previous studies have shown that reducing the expression of ERCC-1 will hinder the repair of DNA damage and cause a variety of oxidative damage and the accumulation of senescent cells [4].

Although the mice were knocked out of ERCC-1 in their immune organs, they were still able to be born and grow up normally, and they did not show any difference before they reached adulthood.

However, when tested at 8-10 months, it can be found that the level of DNA oxidative damage in the spleen and bone marrow tissues of the mice has increased significantly.

Longitudinal comparison of young self, the number of T cells and B cells in knockout ERCC-1 mice was significantly reduced; horizontal comparison of normal mice, the count of lymphocytes in knockout mice was also more unstable.

The researchers believe that this is enough to show that what occurs in ERCC-1 knockout mice is not an immune "developmental defect", but an immune "degeneration".

To put it in a more popular way, the immune system of ERCC-1 knockout mice has aged prematurely! When compared with normal 2-year-old aging mice, it can also be found that the immune cells of knockout mice are somewhat similar to those of naturally aging immune cells.

Subsequent analysis of immune cell subsets also showed that the SASP phenotype of T cells, NK cells and macrophages in knockout mice was significantly increased, similar to normal aging.

Compared with normal mice (blue), the immune cell characteristics of ERCC-1 knockout mice (red) are similar to those of normal aging mice (yellow).
So what is the effect of aging of the immune system? Immune function decline is affirmative.

The researchers also collected a variety of tissues from 8-11 months old knockout mice for analysis, and found that high levels of DNA damage, oxidative stress, and aging occurred in non-lymphatic organs! These further lead to tissue damage.

For example, serum liver injury markers alanine and aspartate aminotransferase are elevated, urine albumin and kidney injury markers are elevated, and pancreatic dysfunction marker amylase levels are elevated.

Needless to say, the life span of ERCC-1 knockout mice has also become shorter.

Many tissues show aging and damage to the immune system.
The lifespan of aging mice is shortened.
When the researchers transplanted spleen cells from ERCC-1 knockout mice to mice with progeria, the poor mice deteriorated and their lifespans were shorter.

Conversely, transplanting spleen cells from young healthy mice to premature aging mice, and testing one month later, it can be found that the expression of senescence markers in several tissues is significantly reduced, and the SASP-related cytokines in the blood circulation are also reduced.

After transplantation of immune cells in young mice (orange) cell senescence characteristics were significantly reduced.
Previous studies have found that inhibiting mTOR activity with rapamycin analogs can enhance the response of the elderly to influenza vaccine [5], so researchers also tried to use rapamycin In treatment of ERCC-1 knockout mice, it was found that it can significantly reduce the expression of aging markers in peripheral immune cells and improve the immune function of mice.

This shows that targeting senescent immune cells is indeed very promising.

Although we should shout for a blood exchange to fight aging and hurry up at this time, but think about it carefully, there is such a way to trade youth, I am afraid we are exporting youth.
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So let's hurry up with new targets and new drugs! Reference: [1] Kirkland, JL & Tchkonia, T.
Cellular senescence: a translational perspective.
EBioMedicine 21, 21–28 ( 2017).
[3] Goronzy, JJ & Weyand, CM Understanding immunosenescence to improve responses to vaccines.
Nat.
Immunol.
14, 428–436 (2013).
[4] Robinson, AR et al.
Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging.
Redox Biol.
17, 259–273 (2018).
[5] Mannick, JB et al.
TORC1 inhibition enhances immune function and reduces infections in the elderly.
Sci.
Transl.
Med.
10, eaaq1564 (2018).
The author of this article | Dai Siyu