Senescent Cell Presence in Skin Correlates with Skin Aging

Researchers here show that a greater number of senescent cells in skin correlates with a greater loss of skin elasticity. As we age, skin becomes less elastic. Damage to the structures of the extracellular matrix that determines this and other physical properties of tissue occurs due to a number of processes, such as cross-linking and the activities of senescent cells. Developing methods to remove cross-links and clear senescent cells would allow the production of therapies to reverse these and numerous other issues associated with aging:

Senescent cells are more prevalent in aged human skin compared to young, but evidence that senescent cells are linked to other biomarkers of aging is scarce. We counted cells positive for the tumor suppressor and senescence associated protein p16INK4a in sun-protected upper-inner arm skin biopsies from 178 participants (aged 45-81 years) of the Leiden Longevity Study. Local elastic fiber morphology, facial wrinkles, and perceived facial age were compared to tertiles of p16INK4a counts, while adjusting for chronological age and other potential confounders.

The numbers of epidermal and dermal p16INK4a positive cells were significantly associated with age-associated elastic fiber morphologic characteristics, such as longer and a greater number of elastic fibers. The p16INK4a positive epidermal cells (identified as primarily melanocytes) were also significantly associated with more facial wrinkles and a higher perceived age. Participants in the lowest tertile of epidermal p16INK4a counts looked 3 years younger than those in the highest tertile, independently of chronological age and elastic fiber morphology.

In conclusion, p16INK4a positive cell numbers in sun-protected human arm skin are indicative of both local elastic fiber morphology and the extent of aging visible in the face.



That is a bit depressing that low levels of senescent cells in the skin only made people look 3 years younger.

Posted by: Jim at August 20th, 2015 11:24 AM

It depends on ratio between highest and lowest levels.

Posted by: Martin S. at August 20th, 2015 12:25 PM

Jim, I bet their assessment of the subjects' external youthfulness was quite subjective. "Looked 3 years younger": there's only so much one can do to quantify a look.

Posted by: Nico at August 20th, 2015 12:36 PM

Jim, as I understand it, but I could be wrong, the biggest factor in skin aging (or at least wrinkles) is cross-links (AGEs) and not senescent cells, so removing or having fewer senescent cells naturally won't make much difference.

Posted by: Northus at August 20th, 2015 2:35 PM

What do you guys think - Clear senescent cells and then temporary telomerase therapy, or the other way around? Question intended mainly for Steve H, who I know is lurking hereabouts somewhere.

Posted by: Seth at August 20th, 2015 2:56 PM

@Nico: People at the cosmetic industry measure skin hydration with a corneometer. Maybe there is an equivalent device for skin stiffness.

Posted by: Antonio at August 20th, 2015 4:56 PM

The following paper indicates that fibroblast senescence may be reversed when they are placed in a younger extracellular matrix --
"Restoration of senescent human diploid fibroblasts by modulation of the extracellular matrix";jsessionid=0FD687133A7389273A72BEB612A8B1E6.f04t04

Possibly also of interest are the following --
"Human Dermal Stem/Progenitor Cell-Derived Conditioned
Medium Improves Senescent Human Dermal Fibroblasts"

"Gamma-tocotrienol modulation of senescence-associated gene expression prevents cellular aging in human diploid fibroblasts"

Posted by: Lou Pagnucco at August 20th, 2015 9:13 PM

Seth: I am lurking around yes :)

I would think the best idea would be to transiently induce telomerase and recover the significant number of cells that are perfectly capable of working. Follow up with Senlyotics to remove the rogue cells sitting there sending out SASP.

Senescence has been shown to be far more complex than thought before and there are differing levels of it, some cells can be returned to duty and are almost as good as new. This is based on the work by the Conboys and their comments to that effect.

Regarding skin metrics a punch biopsy would be a good start with illumina 450k assay to measure changes to gene expression profile. You could use that data to measure collagen 1 and 3 production too which would give a good indication of elasticity. Some of the skin industry standard tests could provide useful secondary evidence.

Though an artificial construct in this example the original Geron telomerase skin rejuvenation test has methodology that could be useful here too:

Posted by: Steve H at August 21st, 2015 9:50 AM
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