Patterns of Natural Aging and the Role of Senescence Registry
Condition: Healthy Aging
Study type: Observational

Summary: 
      This is a registry to identify changes in the expression of aging-related biomarkers, changes
      in functional performance, and/or changes in quality-of-life across the aging spectrum in 250
      participants ≥ 25 years of age that will be conducted by the University of North Carolina.
      The primary purpose of this registry is to measure biomarkers of aging/senescence and build
      computational models of aging in order to better understand the role of senescence in
      aging-related functional decline and differences between aging in a general population vs
      cohorts enriched for aging related disease (cancer, heart disease). Aging biomarker data in
      cohorts with cancer and heart disease has already been collected; the current study will
      enroll participants into the cohort of aging in the general population (Aging Cohort).

      Over the past century, life expectancy has increased by 30 years. With that gain has come a
      dramatic rise in age-related disease and an urgent need to understand, prevent, and treat
      these conditions. While age-related diseases have diverse phenotypes, there is increasing
      recognition of common biological underpinnings with cellular senescence as the nexus linking
      subcellular changes due to epigenetic changes, DNA damage, and mitochondria dysfunction with
      a decline in health due to multi-morbidity. The molecular changes that shift one's aging
      trajectory from a 'healthy' state to a 'disease' state are poorly understood; however, there
      is increasing evidence that senescence plays a key role in this shift. Computational models
      of natural aging and aging related disease are important tools in understanding the
      phenomenon of senescence, its regulation and dynamics, and its role in physiological or
      pathological processes during human aging. These findings will serve as pilot data for future
      analysis of cellular senescence, as measured by p16INK4 (hereafter referred to as p16)
      expression, and aging in other cohorts and begin to establish comparisons between p16 and
      other potentially clinically relevant aging biomarkers such as DNA methylation and plasma
      proteomics.
    

Detailed description: 
      The primary purpose of this registry is to collect aging biomarker data in a general
      population across the entire lifespan (Aging Cohort). The investigators will then build
      several computational models of aging in order to better understand senescence in the context
      of general aging or specific aging associate diseases. As a secondary goal, The investigators
      will determine the association between biomarkers of aging and health characteristics
      (defined through blood chemistry panels and specific functional measures). Central to these
      computational models is the measurement of a biomarker of aging/senescence, p16INK4
      (hereafter referred to as p16) in peripheral blood T cells. The primary aim of this registry
      is to determine if p16 mRNA expression measured in T cells reflects total organismal
      senescent load. The secondary aim is to determine if senescence dynamics are affected by
      age-associated chronic diseases. The exploratory aim is to determine the ability of
      computational models of senescence to predict clinical and functional status. Active
      participation in the study will end at the completion of the study questionnaires and
      assessments, but The investigators will ask permission to recontact participants at a later
      date for longitudinal sample collection.

      Despite the prominence of senescence as an aging mechanism and target of geroscience-based
      therapies, little is known about the dynamics of senescent cells in humans. Understanding the
      process of senescence, including its regulation, dynamics, and contribution to physiologic or
      pathologic processes, is essential for an understanding of aging.

      In this registry, the investigators will assess the contribution of senescence,
      co-morbidities, functional performance, and quality of life to aging. The investigators will
      determine the ability of these factors to aid in the development of a new stochastic model
      that will be formulated specifically in the context of T-cell turnover and senescence,
      thereby providing a cell level description of p16 accumulation and a mechanistic model with
      parameters characterizing relevant physiological processes. The development of this new model
      will thus enable a quantitative, predictive, mechanistic study of the role of senescence in
      aging at both organismal and cellular levels
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        "Healthy" adults age 18 to 85 who meet inclusion criteria and do not have exclusion
        criteria.

        It is a convenience sample.
      
Biospecimen description: 
      The study will determine the association between biomarkers of aging and health
      characteristics (defined through blood chemistry panels and specific functional measures).
      Central to these computational models is the measurement of a biomarker of aging/senescence,
      p16INK4 (hereafter referred to as p16) in peripheral blood T cells. The primary aim of this
      registry is to determine if p16 mRNA expression measured in T cells reflects total organismal
      senescent load. The secondary aim is to determine if senescence dynamics are affected by
      age-associated chronic diseases.