The current available senescent cell biomarkers are limited, and their accuracy is not ideal, so the arrival of better biomarkers that can do a better job are a welcome addition to the field. The current methods for detecting senescent cells leave a lot to be desired and have seen little innovation in the last decade or more. In order to develop effective repair-based therapies that address the aging processes, we need far better biomarkers that can accurately show that these interventions work.
For example, CellAge, hosted with us at Lifespan.io, is developing a biomarker for senescent cells in order to help researchers more effectively quantify therapies that remove these cells.
What are senescent cells?
Cellular senescence is one of a number of processes that cause you to age, which are known collectively as the hallmarks of aging . As you age, an increasing number of your cells become senescent. These senescent cells no longer divide or support the tissues of which they are part; instead, they send out a cocktail of harmful chemical signals (cytokines) that cause inflammation and thus drive aging processes and the onset of age-related diseases.
This proinflammatory cocktail of cytokines and signals is known as the senescence associated secretory phenotype (SASP). The SASP blocks various important cellular processes, prevents stem cells from repairing damaged tissue efficiently, and is implicated in the development of various age-related diseases [2-3].
If that was not bad enough, SASP from senescent cells can also encourage other nearby healthy cells to become senescent just like them. This means that a small number of these cells can have a dramatic effect. This ultimately leads to a downward spiral of increasingly poor tissue repair and the onset of age-related diseases.
Ok, so senescent cells are bad, right?
Yes and no. It has been suggested that cellular senescence contributes to aging because the amount of senescent cells increase with it. However, this is not quite as simple as it first appears and downplays what the main purpose of cellular senescence is. Senescence is a safety feature built into cells to prevent the propagation of damaged cells, allowing them to enter apoptosis (cell death) and have the immune system dispose of them. Therefore, senescence is, generally speaking, a good thing, as it keeps us safe from damaged cells causing cancer and promotes healthy tissue repair.
However, there is a tipping point in this safety checkpoint. Clearing away unwanted senescent cells is the job of the immune system, and replacing the lost cells requires stem cells to repopulate the tissue. As we get older, the ability of our immune system to clear these cells begins to fail, and they begin to accumulate; this, in turn, increases inflammation, reducing the ability of stem cells to replace losses and further reducing the ability of the immune system to function, causing a vicious circle. At this point, cellular senescence ceases to be a safety checkpoint and switches to becoming an active driver of aging processes.
A novel approach to senescent cell detection
A new research study by Zorin et al. discusses using skin samples as the basis for a novel approach to measuring the level of senescent cells in a patient. . The researchers focus on dermal fibroblasts and why they are one of the most numerous and important types of cell in the skin. Fibroblasts are responsible for multiple functions in the skin, including maintaining its structural integrity and helping to maintain the physiological condition of other skin layers.
Fibroblasts help maintain the integrity of the skin by remodelling and renewing its structure, disposing of damaged dermal components and creating new ones; this includes the creation of collagen and elastin. However, as we age, the numbers of fibroblasts in the skin declines along with their ability to recycle and produce dermal components to maintain skin structure. Thinning skin, loss of flexibility and elasticity, as well as the formation of wrinkles, are visual indicators of this failing ability to maintain skin structure. These researchers suggest that evaluating the proliferative potential of dermal fibroblasts would be a suitable biomarker for skin aging and for assessing the effect of treatments that attempt to address skin aging.
Measuring the ability of cells to form colonies in vitro is a typical method for assessing their survival and was originally used to evaluate the decline of reproductive capacity of cells after exposure to damaging agents. Researchers later found that cells isolated via biopsy had varying ability for colony formation between different individuals. This allows for comparisons of proliferative capacity between different patients’ cells, as the density of colony formation predicts the capacity of those cells.
The researchers found that dense colonies of cells have a smaller number of β-galactosidase positive cells (a biomarker of senescence), are the direct progeny of fibroblast progenitor cells, and have a high replicative capacity. Less dense colonies have a significantly higher number of β-galactosidase positive cells, are likely more distant descendants of the original progenitor cells, and thus have a lower replicative capacity. They noted that the more diffused and less dense a colony is, the more senescent cells it has.
The assessment of skin fibroblast colonies could be a fast and accurate predictor of replicative capacity and cellular senescence, and it could be a useful biomarker to assess the efficacy of senescent cell clearing therapies.
 López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
 Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010). The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression. Annual Review of Pathology, 5, 99–118.
 Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010). Inflammatory Networks during Cellular Senescence: Causes and Consequences. Trends in Molecular Medicine, 16(5), 238–246.
 Zorin V, Zorina A, Smetanina N, Kopnin P, Ozerov IV, Leonov S, Isaev A, Klokov D, Osipov AN. Diffuse colonies of human skin fibroblasts in relation to cellular senescence and proliferation. Aging (Albany NY). 2017 May 16. doi: 10.18632/aging.101240.