Midlife Pace of Aging in the Dunedin Study

生育率的下降、婴儿潮一代的老龄化、预期寿命的延长正在导致人口老龄化。随着人口老龄化，这增加了与年龄有关的疾病的公共卫生负担，如心血管疾病、2型糖尿病和痴呆症。事实证明，在晚年治疗无法预防的疾病既昂贵又无效。现在已经知道，与年龄有关的疾病的潜在可预防的风险暴露和生理原因出现在儿童时期。这一认识为从儿童时期开始跟踪研究提供了新的科学意义。现在也知道，与年龄有关的疾病的发病机制涉及器官系统的逐渐累积衰退，始于生命历程的前半段。因此，旨在预防与年龄有关的疾病的新干预措施必须在个人还年轻、步入中年之前应用于他们。将老年学的基础科学发现转化为针对年轻人的预防性干预措施是缺乏的，因为在生命的前半段，人们对生物衰老的过程几乎一无所知。这促使我们提出从20多岁开始研究生物衰老速度的建议。我们将使用达尼丁多学科健康与发展研究，这是一项对现已进入第五个十年的出生队列的纵向研究。这项研究结合了人口/经济调查、临床质量健康评估、生物银行以及与全国行政记录（健康、福利、财政）的联系等方法。我们建议对1004名出生队列的在世成员实施全天数据收集方案。为了评估每个队列成员的生物衰老速度，我们将：(a)测量多个器官系统的生物标志物，(b)在26岁、32岁、38岁和45岁时评估这些生物标志物的相关变化的统计模型。我们将描述衰老速度的个体差异，以及其发育起源、基因组特征、功能后果、相关认知变化和经济成本。我们将识别出那些身体比实际年龄年轻几个月或几年的个体的特征。拟议的工作将通过产生支持未来中年或早期干预措施的发现来提高知识，以减缓衰老，预防与年龄有关的疾病，并提高长寿的质量。

Declining fertility rates, aging of the baby-boomers, and increasing life expectancy are leading to population aging. As the population ages, this increases the public-health burden of age-related conditions, such as cardiovascular disease, type 2 diabetes, and dementia. Treating un-prevented diseases in late life has proven costly and ineffective. It is now known that potentially preventable risk exposures and physiological causes of age-related disease emerge in childhood. This recognition lends new scientific significance to studies that have followed cohorts from childhood. It is also now known that the pathogenesis of age-related diseases involves gradually accumulating decline in organ systems, beginning in the first half of the life course. Consequently, new interventions aiming to prevent age-related diseases will have to be applied to individuals while they are yet young, before they reach midlife. Translation of basic-science gerontology discoveries into preventive interventions for young humans is lacking because virtually nothing is known about the process of biological aging during the first half of the life course. This prompts our proposal to study the pace of biological aging from the twenties forward. We will use the Dunedin Multidisciplinary Health & Development Study, a longitudinal study of a birth cohort now entering its fifth decade. This study combines methods of demographic/economic surveys, clinical-quality health assessments, biobanking, and linkage to nationwide administrative records (health, welfare, finances). We propose to administer a full-day data-collection protocol to the 1004 living members of the birth cohort. To assess each cohort member's pace of biological aging we will: (a) measure biomarkers across multiple organ systems, and (b) statistically model correlated change in these biomarkers assessed at ages 26, 32, 38, and 45 years. We will describe individual variation in the pace of aging, plus its developmental origins, genomic signatures, functional consequences, associated cognitive changes, and economic costs. We will identify attributes that set apart individuals whose bodies are months or years younger than their chronological age. The proposed work will improve knowledge by generating findings to support future interventions during midlife or earlier, to slow aging, prevent age-related disease, and improve the quality of longer lives.