What do you all think are the key indicators of senescence levels? Ie, are there certain markers we could track in blood tests? Other tests? And whatever that is, how do we determine whether it’s good, bad or inert? I searched all the posts mentioning senescence, but none seem to address this. This seems to me like a critical variable to track and attempt to affect.
Scientific papers talk as though there is a way to identify and track (senescent cell loads etc.). I think they track another protein that is associated with autophagy in the context of whether a drug is reducing senescent load but not sure how senescence apart from autophagy is measure. Other brighter minds on here will know, Also interested, good question.
Here’s what Bing’s AI said:
There are several markers that can be used to detect cellular senescence, such as SABG, p21, and p16 1. However, these markers have limitations and novel non-invasive approaches are needed to detect cellular senescence with high sensitivity and specificity 1. A blood test for inflammatory and cell senescence biomarkers may be a reliable predictor of cognitive decline 2.
But when I asked how one conducts such a test, it could find absolutely nothing. From what I’ve gleaned in the various journals, all the tests are essentially biopsy microscopy. Not exactly non-invasive.
CRP responds to IL-6 which is part of SASP. However, IL-6 is also increased by infection. Hence if you wish to use CRP as an indicator of the senescent cell load you need to take a number of readings at different times and pick the lowest. Ideally at a time when you know you have not recently been infected.
I can see how high CRP might point to senescence. But, it’s not clear to me that low CRP suggests less senescence.
Its a guide to levels of SASP
Start by reviewing the following;
I already reviewed both of those. Before I posted this question I did a review of the literature. The problem is not that there is a shortage of speculation about senescence-correlated phenomena. But, whether telomere length or the bio-markers in tumors, neither points to a clear assay one can easily do. I am interested in blood test mentioned earlier in the thread. But I am also skeptical about what it reveals. Inflammation is, again, often correlated to senescence. But, does a lack of inflammation imply little senescence? This may be a question without an answer—or maybe there is some more precise marker.
Some of the literature on Parkinson’s Disease addresses this explicitly. But it’s not clear how to use the tests they recommend since the ranges are all pegged to normal vs. “likely to develop PD”. There isn’t a normative standard for non-pathological testing.
Then, there’s this rather interesting kit. Not sure what to make of it. And I’m not even sure what it tests, eg, blood, urine, biopsy, other? All of this makes me wish I had continued in to medical school after pre-med… but, “when two paths diverge”…. I took the other,
One of the challenges with this is that there are a number of different types of senescence and we are some way away from working out exactly what is going on.
It appears to me that a key aspect of senescence occurs when cells don’t properly differentiate. That it appears is a cause of a number of age based diseases and some of the best evidence for this relates to osteoporosis.
The good thing about the CRP test is that it is not invasive and quite cheap.
A limitation, however, is that most CRP tests have a lower threshold that is a bit of a nuisance.
If you have not reviewed, see;
The footnote to your post points to telomere length, p21 and p16.
Researchers analyzed whether markers of cellular senescence such as telomere length (TL), p16 and p21 expression, as well as inflammatory markers in blood samples taken close to diagnosis can be predictive of cognitive and motor progression of the disease over the next 36 months. Mean leukocyte TL and the expression of senescence markers p21 and p16 were measured at two time points (baseline and 18 months). Investigators also selected five inflammatory markers from existing baseline data.
The galactosidase kit seems to be a test for cell or tissue samples, not a blood test.
Number 1: β-Galactosidase Staining Kit
Senescent cells are known to express β-Galactosidase in a pH-dependent fashion, specifically detectable at pH 61. Our comprehensive Senescence β-Galactosidase Staining Kit #9860 contains everything you need to detect β-galactosidase activity at pH 6 in cells—or even frozen tissue. Perfect for quickly and easily testing multiple cell populations or tissue samples, the directions are straightforward, and the blue staining is bright and clear.
Inflammation seems to be a good substitute test, as John Hemming opines.
my company measures cellular senescence in blood. not available commercially yet but we have measured it in thousands of people, including ~500 participants without comorbidities to establish “healthy aging” thresholds
How, general information?
That’s interesting. Any work on measuring the effect of interventions to reduce senescence?
That’s precisely where we are going with this. Work in progress and we are blinded to interventions but senescence can be moved which actually surprised us. It is very stable otherwise
One of the best ways I have heard of to measure senescence is to measure IL-6. This is found in the SASP released by inflammatory senescent cells. (And you can avoid counting the non inflammatory less harmful non-SASP releasing senescent cells.)
A particular emphasis is made on pro-inflammatory cytokines (IL-6 and IL-8) secreted by senescent/inflammatory cells, known to induce EMT, cell migration, and de-differentiation, and be responsible for propagating senescence and inflammation in the TME.
IL-6 causes the creation of CRP.
Hence you can also measure CRP. They both have the problem caused by bacterial infections so you need a number of measurements.
It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via C1q.