Some of our closest invertebrate cousins, like this Acorn worm, have the ability to perfectly regenerate any part of their body that’s cut off — including the head and nervous system. Humans have most of the same genes, so scientists are trying to work out whether human regeneration is possible, too.

Regeneration – now that’d be a nice superpower to have. Injure an arm? Chop it off and wait for it to grow back. Dicky knee? Ingrown toenail? Lop off your leg and get two for one!

It sounds ridiculous, but there’s a growing number of scientists that believe body part regeneration is not only possible, but achievable in humans. After all, not only are there plenty of animals that can do it, we can do it ourselves for our skin, nails, and bits of other organs.

Cellular senescence is a diverse phenotype characterised by permanent cell cycle arrest and an associated secretory phenotype (SASP) which includes inflammatory cytokines. Typically, senescent cells are removed by the immune system, but this process becomes dysregulated with age causing senescent cells to accumulate and induce chronic inflammatory signalling. Identifying senescent cells is challenging due to senescence phenotype heterogeneity, and senotherapy often requires a combinatorial approach. Here we systematically collected 119 transcriptomic datasets related to human fibroblasts, forming an online database describing the relevant variables for each study allowing users to filter for variables and genes of interest. Our own analysis of the database identified 28 genes significantly up-or downregulated across four senescence types (DNA damage induced senescence (DDIS), oncogene induced senescence (OIS), replicative senescence, and bystander induced senescence) compared to proliferating controls. We also found gene expression patterns of conventional senescence markers were highly specific and reliable for different senescence inducers, cell lines, and timepoints. Our comprehensive data supported several observations made in existing studies using single datasets, including stronger p53 signalling in DDIS compared to OIS. However, contrary to some early observations, both p16 and p21 mRNA levels rise quickly, depending on senescence type, and persist for at least 8–11 days. Additionally, little evidence was found to support an initial TGFβ-centric SASP. To support our transcriptomic analysis, we computationally modelled temporal protein changes of select core senescence proteins during DDIS and OIS, as well as perform knockdown interventions. We conclude that while universal biomarkers of senescence are difficult to identify, conventional senescence markers follow predictable profiles and construction of a framework for studying senescence could lead to more reproducible data and understanding of senescence heterogeneity.

Multiple studies now suggest that the accumulation of senescent cells is causal in ageing (Childs et al., 2015; Mylonas and O’Loghlen, 2022; van Deursen, 2014; Wlaschek et al., 2021), and their ablation extends healthspan and mean lifespan in rodents (Baker et al., 2016; Baker et al., 2011). Novel senolytic and senostatic drugs are in development (Kim and Kim, 2019; Niedernhofer and Robbins, 2018) with some drugs in clinical trials (Hickson et al., 2019; Justice et al., 2019) which might shortly lead to treatments capable of improving healthspan and extending lifespan in humans. However, the exact nature of senescent cells is often difficult to define, with multiple studies indicating that the most common biomarkers of senescence show different profiles across cell lines, types of senescence inducer, and the timepoint after the initial stimulus (Avelar et al., 2020; Basisty et al., 2020; Casella et al., 2019; Hernandez-Segura et al., 2017; Neri et al., 2021).