Volume 7, Issue 5

Horvath S, Mah V, Lu AT, Woo JS, Choi O, Jasinska AJ, Riancho JA, Tung S, Coles NS, Braun J, Vinters HV, Coles LS, . The cerebellum ages slowly according to the epigenetic clock. . 7:294-306. https://doi.org/10.18632/aging.100742

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                TY  - JOUR
                AU  - Horvath, Steve 
                AU  - Mah, Vei 
                AU  - Lu, Ake T. 
                AU  - Woo, Jennifer S. 
                AU  - Choi, Oi-Wa 
                AU  - Jasinska, Anna J. 
                AU  - Riancho, José A. 
                AU  - Tung, Spencer 
                AU  - Coles, Natalie S. 
                AU  - Braun, Jonathan 
                AU  - Vinters, Harry V. 
                AU  - Coles, L. Stephen 
                TI  - The cerebellum ages slowly according to the epigenetic clock
                JO  - 
                JA  - 
                VL  - 7
                IS  - 5
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100742
                DO  - 10.18632/aging.100742
                SP  - 294
                EP  - 306
                PY  - 
                AB  - Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2×10−9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8×10−3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases.
                ER  -

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Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila

Joung-Sun Park, Hyun-Jin Na, Jung-Hoon Pyo, Ho-Jun Jeon, Young-Shin Kim, Mi-Ae Yoo,

https://doi.org/10.18632/aging.100743 pp 307—318

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Park J, Na H, Pyo J, Jeon H, Kim Y, Yoo M, . Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila. . 7:307-318. https://doi.org/10.18632/aging.100743

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                TY  - JOUR
                AU  - Park, Joung-Sun 
                AU  - Na, Hyun-Jin 
                AU  - Pyo, Jung-Hoon 
                AU  - Jeon, Ho-Jun 
                AU  - Kim, Young-Shin 
                AU  - Yoo, Mi-Ae 
                TI  - Requirement of ATR for maintenance of intestinal stem cells in aging <i>Drosophila</i>
                JO  - 
                JA  - 
                VL  - 7
                IS  - 5
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100743
                DO  - 10.18632/aging.100743
                SP  - 307
                EP  - 318
                PY  - 
                AB  - The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adult Drosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.
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Biological ageing and frailty markers in breast cancer patients

Barbara Brouwers, Bruna Dalmasso, Sigrid Hatse, Annouschka Laenen, Cindy Kenis, Evalien Swerts, Patrick Neven, Ann Smeets, Patrick Schöffski, Hans Wildiers,

https://doi.org/10.18632/aging.100745 pp 319—333

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Brouwers B, Dalmasso B, Hatse S, Laenen A, Kenis C, Swerts E, Neven P, Smeets A, Schöffski P, Wildiers H, . Biological ageing and frailty markers in breast cancer patients. . 7:319-333. https://doi.org/10.18632/aging.100745

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                TY  - JOUR
                AU  - Brouwers, Barbara 
                AU  - Dalmasso, Bruna 
                AU  - Hatse, Sigrid 
                AU  - Laenen, Annouschka 
                AU  - Kenis, Cindy 
                AU  - Swerts, Evalien 
                AU  - Neven, Patrick 
                AU  - Smeets, Ann 
                AU  - Schöffski, Patrick 
                AU  - Wildiers, Hans 
                TI  - Biological ageing and frailty markers in breast cancer patients
                JO  - 
                JA  - 
                VL  - 7
                IS  - 5
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100745
                DO  - 10.18632/aging.100745
                SP  - 319
                EP  - 333
                PY  - 
                AB  - Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients
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Epigenetic age analysis of children who seem to evade aging

Richard F. Walker, Jia Sophie Liu, Brock A. Peters, Beate R. Ritz, Timothy Wu, Roel A. Ophoff, Steve Horvath,

https://doi.org/10.18632/aging.100744 pp 334—339

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Walker RF, Liu JS, Peters BA, Ritz BR, Wu T, Ophoff RA, Horvath S, . Epigenetic age analysis of children who seem to evade aging. . 7:334-339. https://doi.org/10.18632/aging.100744

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                TY  - JOUR
                AU  - Walker, Richard F. 
                AU  - Liu, Jia Sophie 
                AU  - Peters, Brock A. 
                AU  - Ritz, Beate R. 
                AU  - Wu, Timothy 
                AU  - Ophoff, Roel A. 
                AU  - Horvath, Steve 
                TI  - Epigenetic age analysis of children who seem to evade aging
                JO  - 
                JA  - 
                VL  - 7
                IS  - 5
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100744
                DO  - 10.18632/aging.100744
                SP  - 334
                EP  - 339
                PY  - 
                AB  - We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other such cases exist, and if so, whether aging is actually slowed. Of seven children characterized by dramatically slow developmental rates, five also had associated disorders displayed by the first case. All of the identified subjects were female. To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as “epigenetic clock” based on DNA methylation levels. No statistically significant differences in chronological and epigenetic ages were detected in any of the newly discovered cases. Our study shows that a) there are multiple children who maintain the façade of persistent toddler-like features while aging from birth to young adulthood and b) blood tissue from these cases is not younger than expected.
                ER  -

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Volume 7, Issue 5

Editorials

Biomarkers and subtypes of cancer

Maud H.W. Starmans, Paul C. Boutros,

Reactive resistance to anti-angiogenic drugs

Guilhem Bousquet, Anne Janin,

BATF2 in human colorectal cancer

Zebing Liu, Yu Yang, Xiaoyan Zhou,

Zebrafish in oncology

Jorge Barriuso, Raghavendar Nagaraju, Adam Hurlstone,

Personalized virotherapy in cancer

Eduardo G. Cafferata, Osvaldo L. Podhajcer,

A piece of the ‘chemobrain’ puzzle: pNF-H

Akina Natori, Toru Ogata, Hideko Yamauchi,

Aspirin and prostate cancer prevention

Adriana C. Vidal, Stephen J. Freedland,

Research Papers

The cerebellum ages slowly according to the epigenetic clock

Steve Horvath, Vei Mah, Ake T. Lu, Jennifer S. Woo, Oi-Wa Choi, Anna J. Jasinska, José A. Riancho, Spencer Tung, Natalie S. Coles, Jonathan Braun, Harry V. Vinters, L. Stephen Coles,

Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila

Joung-Sun Park, Hyun-Jin Na, Jung-Hoon Pyo, Ho-Jun Jeon, Young-Shin Kim, Mi-Ae Yoo,

Biological ageing and frailty markers in breast cancer patients

Barbara Brouwers, Bruna Dalmasso, Sigrid Hatse, Annouschka Laenen, Cindy Kenis, Evalien Swerts, Patrick Neven, Ann Smeets, Patrick Schöffski, Hans Wildiers,

Epigenetic age analysis of children who seem to evade aging

Richard F. Walker, Jia Sophie Liu, Brock A. Peters, Beate R. Ritz, Timothy Wu, Roel A. Ophoff, Steve Horvath,

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