Overexpression of Mitochondrial Peptide Humanin as a Potential Approach to Slowing Aging

Researchers have discovered a number of mitochondrial peptides that influence cell and tissue health. Here, it is demonstrated that upregulation of humanin is sufficient to extend life in nematode worms. Since humanin levels decrease with age, and since long-lived families tend to have higher levels of humanin, it is hoped that upregulation can be the basis for therapies to modestly slow the progression of aging. There has been a fair amount of research along these lines in recent years, such as showing that delivery of humanin improves cognition in aged mice. It is an interesting part of the field.

Humanin is a member of a new family of peptides that are encoded by short open reading frames within the mitochondrial genome. Humanin is the first member of this new class of mitochondrial-derived signaling peptides that now includes MOTS-c and SHLP1-6. The humanin gene is found as a small open reading frame within the 16s rRNA gene of the mitochondrial genome. It is highly conserved in chordates but can also be found in species as distant as the nematode, suggesting that humanin is an ancient mitochondrial signal used to communicate to the rest of the organism.

Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence.

Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease. Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.

Link: https://doi.org/10.18632/aging.103534


So far all we can do is try to replenish declining levels of various things that decline for some reason. Ideally we should focus on why all these things suddenly start declining and what is happening to cause this. Is it programmed or is it damage or a build up of junk, some kind of signal that goes off or all the above and more? It seems way too costly to just try and upkeep everything that is declining with age and instead address the problem at its root.

Posted by: Nate at July 1st, 2020 10:05 AM

Nate, that is what 'they' are working toward. It is a journey of discovery taken one step at a time

Posted by: JohnD at July 1st, 2020 1:46 PM

Any deficiency which has downstream pathology is a bow hanging fruit to do a
marginal improvement . Like controlling good pressure and cholesterol levels. You don't address the root cause but nevertheless reduce the downstream damage. A small crouch here, a little push there and all the effects can add up to a couple of decades of extra healthy (less sick) life.

It is a small step but if you make hundreds of those and each one adds on average only a couple of months to the health span the aggregate result cold still be impressive and buy you enough time to stick around for the first real treatments to be available.

Posted by: Cuberat at July 1st, 2020 8:29 PM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.