Summary: Senescent cells produce and secrete various bioactive molecules including interleukins, growth factors, matrix‐degrading enzymes and reactive oxygen species (ROS). Thus, it has been proposed that senescent cells can damage their local environment, and a stimulatory effect on tumour cell growth and invasiveness has been documented. However, it was unknown what effect, if any, senescent cells have on their normal, proliferation‐competent counterparts. We show here that senescent cells induce a DNA damage response, characteristic for senescence, in neighbouring cells via gap junction‐mediated cell–cell contact and processes involving ROS. Continuous exposure to senescent cells induced cell senescence in intact bystander fibroblasts. Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo.

It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Objectives The Newcastle 85+ Study aims to systematically study the clinical, biological, and psychosocial attributes of an unselected cohort of 85 year olds and to examine subsequent health trajectories as the cohort ages; health at baseline is reported. Design Cross sectional analysis of baseline data from a cohort study. Setting Newcastle upon Tyne and North Tyneside primary care trusts, United Kingdom. Participants 1042 people born in 1921 and registered with the participating general practices. Main outcome measures Detailed health assessment and review of general practice records (disease, medication, and use of general practice services); participants could decline elements of the protocol. Results Of the 1453 eligible people, 851 (58.6%) were recruited to health assessment plus record review, 188 (12.9%) to record review only, and 3 (0.2%) to health assessment only. Data from record review are reported on a maximum of 1030 and from health assessment on a maximum of 853; individual denominators differ owing to withdrawal and missing values. Of the health assessment sample (n=853), 62.1% (n=530) were women and 10.4% (n=89) were in institutional care. The most prevalent diseases were hypertension (57.5%, 592/1030) and osteoarthritis (51.8%, 534/1030). Moderate or severe cognitive impairment was present in 11.7% (96/824) of participants, severe or profound urinary incontinence in 21.3% (173/813), hearing impairment in 59.6% (505/848), and visual impairment in 37.2% (309/831). Health assessment identified participants with possible disease but without a previous diagnosis in their medical record for hypertension (25.1%, 206/821), ischaemic heart disease (12.6%, 99/788), depression (6.9%, 53/772), dementia (6.7%, 56/840), and atrial fibrillation (3.8%, 30/788). Undiagnosed diabetes mellitus and thyroid disease were rare (1%, 7/717 and 6/762, respectively). A median of 3 (interquartile range 1-8) activities of daily living were undertaken with difficulty. Overall, 77.6% (646/832) of participants rated their health compared with others of the same age as good, very good, or excellent. High contact rates in the previous year with general practitioners (93.8%, 960/1024) were recorded. Women had significantly higher disease counts (medians: women 5, men 4; P=0.033) and disability scores (medians: women 4, men 2; P=0.0006) than men, but were less likely to have attended outpatient clinics in the previous three months (women 29% (150/524), men 37% (118/320), odds ratio 0.7, 95% confidence interval 0.5 to 0.9). Conclusions This large cohort of 85 year olds showed good levels of both self rated health and functional ability despite significant levels of disease and impairment. Hypertension, ischaemic heart disease, atrial fibrillation, depression, and dementia may be underdiagnosed. Notable differences were found between the sexes: women outnumbered men and had more disease and disability.