Can You be Biologically Younger than Your Chronological Age? An Overview of Biological Ageing

The ageing of the population is rapidly escalating worldwide irrespective of unpredictable health challenges like climate change, emerging infectious disease, a microbe that develops drug resistance. India is also experiencing rapid socioeconomic progress and urbanization and the result of this demographic transition is population ageing. Even though there is an increase in life expectancy, there is no increase in health span, and thus increased life expectancy leads to ‘expansion of morbidity'. Longer life expectancy with the expansion of morbidity could enforce a challenge to geroscience as well as a substantial health burden and a threat to the national economy. In normal ageing, chronological age equates to biological age but certain disease conditions accelerate biological age. Similarly, intervention with physical activity, anti-ageing nutraceuticals would slow down the rate ageing process and provide powerful benefits for longevity. The current review article is based on MeSH and free-text terms in databases such as PubMed, the Cochrane Library, and Science Direct. This article aims to provide an overview of the concept of biological ageing with emphasis on the pathophysiology of ageing, quantification of biological ageing and the anti-ageing strategies.

Investigating the DNA methylation profile of e-cigarette use

Background Little evidence exists on the health effects of e-cigarette use. DNA methylation may serve as a biomarker for exposure and could be predictive of future health risk. We aimed to investigate the DNA methylation profile of e-cigarette use. Results Among 117 smokers, 117 non-smokers and 116 non-smoking vapers, we evaluated associations between e-cigarette use and epigenome-wide methylation from saliva. DNA methylation at 7 cytosine-phosphate-guanine sites (CpGs) was associated with e-cigarette use at p < 1 × 10–5 and none at p < 5.91 × 10–8. 13 CpGs were associated with smoking at p < 1 × 10–5 and one at p < 5.91 × 10–8. CpGs associated with e-cigarette use were largely distinct from those associated with smoking. There was strong enrichment of known smoking-related CpGs in the smokers but not the vapers. We also tested associations between e-cigarette use and methylation scores known to predict smoking and biological ageing. Methylation scores for smoking and biological ageing were similar between vapers and non-smokers. Higher levels of all smoking scores and a biological ageing score (GrimAge) were observed in smokers. A methylation score for e-cigarette use showed poor prediction internally (AUC 0.55, 0.41–0.69) and externally (AUC 0.57, 0.36–0.74) compared with a smoking score (AUCs 0.80) and was less able to discriminate lung squamous cell carcinoma from adjacent normal tissue (AUC 0.64, 0.52–0.76 versus AUC 0.73, 0.61–0.85). Conclusions The DNA methylation profile for e-cigarette use is largely distinct from that of cigarette smoking, did not replicate in independent samples, and was unable to discriminate lung cancer from normal tissue. The extent to which methylation related to long-term e-cigarette use translates into chronic effects requires further investigation.

No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing

The increasingly compelling data supporting the involvement of immunobiological mechanisms in Major Depressive Disorder (MDD) might provide some explanation forthe variance in this heterogeneous condition. Peripheral blood measures of cytokines and chemokines constitute the bulk of evidence, with consistent meta-analytic data implicating raised proinflammatory cytokines such as IL6, IL1β and TNF. Among the potential mechanisms linking immunobiological changes to affective neurobiology is the accelerated biological ageing seen in MDD, particularly via the senescence associated secretory phenotype (SASP). However, the cellular source of immunobiological markers remains unclear. Pre-clinical evidence suggests a role for peripheral blood mononuclear cells (PBMC), thus here we aimed to explore the transcriptomic profile using RNA sequencing in PBMCs in a clinical sample of people with various levels of depression and treatment response comparing it with that in healthy controls (HCs). There were three groups with major depressive disorder (MDD): treatment-resistant (n = 94), treatment-responsive (n = 47) and untreated (n = 46). Healthy controls numbered 44. Using PBMCs gene expression analysis was conducted using RNAseq to a depth of 54.5 million reads. Differential gene expression analysis was performed using DESeq2. The data showed no robust signal differentiating MDD and HCs. There was, however, significant evidence of elevated biological ageing in MDD vs HC. Biological ageing was evident in these data as a transcriptional signature of 888 age-associated genes (adjusted p < 0.05, absolute log2fold > 0.6) that also correlated strongly with chronological age (spearman correlation coefficient of 0.72). Future work should expand clinical sample sizes and reduce clinical heterogeneity. Exploration of RNA-seq signatures in other leukocyte populations and single cell RNA sequencing may help uncover more subtle differences. However, currently the subtlety of any PBMC signature mitigates against its convincing use as a diagnostic or predictive biomarker.

P–617 Idiopathic early ovarian aging: Do biomarkers of ageing indicate premenopausal accelerated biological ageing in young women with diminished response to ART?

Study question Do young women with idiopathic early ovarian ageing have changes in telomere length and epigenetic age indicating accelerated biological aging? Summary answer The telomere length and epigenetic age were comparable to those in young women with normal ovarian ageing. What is known already Increased risk of several health events usually considered to be age-related such as cardiovascular disease, osteoporosis, over-all morbidity and mortality have been associated with premature and early menopause when compared to the risk in women with normal menopausal age suggesting an accelerated general ageing process associated to early ovarian ageing. It is unclear whether the onset of this process may start before menopause. Study design, size, duration A prospective cohort study. Young women (≤ 37 years) having ART at two Danish Public fertility clinics during the period 2016 to 2018 were divided into two groups dependent on their ovarian reserve status: early ovarian ageing (EOA) (N = 55) and normal ovarian ageing (NOA)( N = 52). Number of oocytes harvested in first and subsequent cycles was used as a marker of ovarian reserve. Blood samples was drawn at time of oocyte retrieval to assess biological age. Participants/materials, setting, methods EOA was defined as ≥ 2 IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with FSH and NOA as ≥ 8 oocytes harvested in minimum 1 cycle. Known causes influencing the ovarian reserve (endometriosis, ovarian surgery, etc.) was reason for exclusion. Relative telomere length (qPCR) and epigenetic age acceleration (DNA methylation levels) were measured in white blood cells as markers of accelerated biological ageing. Main results and the role of chance Relative telomere length was comparable with a mean of 0.46 (± sd 0.12) in the EOA group and 0.47 (0.14) in the normal ovarian ageing group (p = 0.64). The difference of predicted mean epigenetic age and mean chronological age (i.e. epigenetic age acceleration) was, insignificantly, 0.5 years older in the EOA group when compared to the NOA group( (–1.02 years (2.62) and –1.57 years (2.56), respectively, p = 0.27)), but this difference disappeared when adjusting for chronological age. Limitations, reasons for caution Discrete changes in epigenetic age acceleration may not have been captured as the study only had power to detect an age acceleration of ≥ 2 years. Wider implications of the findings: By analysis of biomarkers for ageing in whole blood, we did not find any indications of a premenopausal accelerated aging in young women with idiopathic EOA. Further investigations in a similar cohort of premenopausal women is needed to fully elucidate the potential relationship between premenopausal accelerated biological ageing and EOA. Trial registration number The study was approved by the Danish Data protection Agency (nr 1–16–02–320–14) and the Regional committee on health research ethics of Central Region Denmark (jr.no 1–10–72–142–14).