Impact of early personal-history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan.
Impact of early personal-history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan.
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DOI：
10.1111/acel.12591
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发表时间：
2017-08
期刊：
影响因子：
7.8
通讯作者：
Moffitt TE
中科院分区：
文献类型：
--
作者：
Belsky DW;Caspi A;Cohen HJ;Kraus WE;Ramrakha S;Poulton R;Moffitt TE
延长健康寿命的疗法正准备从实验室动物模型转向人体临床试验。从小鼠到人类的转化将带来挑战，其中包括人类衰老的多因素异质性。为了让临床试验了解这种异质性，我们报告了人类生物衰老的速度与个人历史特征的关系。由于老年保护治疗必须在中年时进行，以防止年龄相关疾病的发生，我们研究了达尼丁研究1972-73出生队列的年轻成年成员（n = 954）。队列成员的衰老速度被测量为多器官系统完整性的协调下降，通过在队列成员年龄为26岁、32岁和38岁时测定的18种生物标志物的重复测量中量化下降率。所研究的儿童期个人病史特征是年龄相关疾病和死亡率的已知预测因子，并在儿童期进行了前瞻性测量。家族长寿、童年社会阶层、不良童年经历以及童年健康、智力和自我控制的个人历史特征都预测了队列成员成年期衰老速度的差异。更多个人历史风险的积累预示着更快的衰老速度。由于抗衰老疗法的试验需要回顾性地确定个人历史，因此我们使用队列成员在成年时的回顾性个人历史报告复制了结果。由于许多试验从临床环境中招募参与者，我们根据电子病历在最近与卫生系统接触的队列亚组中复制了结果。快速、廉价地测量试验参与者的早期个人历史可以使临床试验能够研究谁是试验志愿者，谁坚持治疗，谁对抗衰老疗法有反应。
Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans’ pace of biological aging relates to personal‐history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age‐related disease onset, we studied young‐adult members of the Dunedin Study 1972–73 birth cohort (n = 954). Cohort members’ Pace of Aging was measured as coordinated decline in the integrity of multiple organ systems, by quantifying rate of decline across repeated measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and 38 years. The childhood personal‐history characteristics studied were known predictors of age‐related disease and mortality, and were measured prospectively during childhood. Personal‐history characteristics of familial longevity, childhood social class, adverse childhood experiences, and childhood health, intelligence, and self‐control all predicted differences in cohort members’ adulthood Pace of Aging. Accumulation of more personal‐history risks predicted faster Pace of Aging. Because trials of anti‐aging therapies will need to ascertain personal histories retrospectively, we replicated results using cohort members’ retrospective personal‐history reports made in adulthood. Because many trials recruit participants from clinical settings, we replicated results in the cohort subset who had recent health system contact according to electronic medical records. Quick, inexpensive measures of trial participants’ early personal histories can enable clinical trials to study who volunteers for trials, who adheres to treatment, and who responds to anti‐aging therapies.
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影响因子：
2.9
作者：
Levine, Morgan E.;Crimmins, Eileen M.
通讯作者：
Crimmins, Eileen M.
影响因子：
64.5
作者：
de Cabo R;Carmona-Gutierrez D;Bernier M;Hall MN;Madeo F
通讯作者：
Madeo F
影响因子：
7.7
作者：
Barker, DJP;Eriksson, JG;Osmond, C
通讯作者：
Osmond, C
影响因子：
5.3
作者：
Klemera, P;Doubal, S
通讯作者：
Doubal, S
DOI：
10.1196/annals.1297.091
发表时间：
2004-01-01
期刊：
STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE: WHY GENUINE CONTROL OF AGING MAY BE FORESEEABLE
影响因子：
--
作者：
Gavrilov, LA;Gavrilova, NS
通讯作者：
Gavrilova, NS