Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant. Supporting Information The supporting information is available online at 10.1007/s11427-023-2305-0. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Background More than 30% of cancer patients experience neuropathic pain. Opioids, as standard pain-relief agents, cannot achieve satisfactory outcomes to treat neuropathic cancer pain due to drug resistance and side effects. Meanwhile, gabapentin, a third-generation anticonvulsant drug, has great potential in providing relief for neuropathic cancer pain. However, there is currently no sufficient evidence to support the efficacy of a combination of gabapentin and opioids in ameliorating neuropathic cancer pain. Hence, the aim of the present study was to explore the analgesic efficacy of gabapentin combined with opioids in treating neuropathic cancer pain. Methods PubMed, EMBASE, and Web of Science (Web of Knowledge) were searched for randomized controlled trials and prospective studies via the following keywords: “gabapentin”, “opioid”, “cancer”, and “neuropathic pain”. We used a scale of 0–10 (0 denoting no pain and 10 denoting the worst pain imaginable) to estimate pain intensity and utilized Review Manager 5.3 and Stata12 to analyze data. Results Seven studies meeting our criterion were selected from 110 records that were primarily searched. The mean difference of pooled pain intensity and the 95% confidence interval (CI) was –1.75 (–2.44, –1.07) (P value <0.00001; treatment group versus control group or time to outcome assessment versus baseline). The pain intensity of cancer patients after a combined treatment of gabapentin and opioids was significantly lower than that of patients receiving opioids alone. Conclusions Our meta-analysis showed that gabapentin combined with opioids effectively alleviated neuropathic cancer pain compared with that of opioids alone.

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