Effects of Glycoxidative Stress on Human Aging
Condition: Aging
Study type: Interventional

Summary: 
      Advanced glycation products or AGEs are a heterogeneous group of molecules formed by exposure
      of tissue constituents to high levels of reducing sugars, e.g. glucose. The interaction of
      these compounds with extra- and intra-cellular components may account in part for several
      conditions related to aging. It has recently been recognized that AGEs are also formed during
      the preparation of food by heating, are absorbed into the circulation and become largely
      incorporated into tissue components. Accumulation of these exogenous substances over time
      may, together with those generated endogenously, contribute to the clinical manifestations
      and complications of aging.

      This is an interventional-randomized study in which we are trying to determine whether a diet
      low in AGE can effectively reduce circulating AGE levels, with or without altering oxidation
      or inflammatory markers, in a subset of both young and older subjects , over a period of 4
      months. If positive results are obtained, longer-term prospective studies will be designed to
      determine if this intervention can affect disease outcomes in older age subjects.

      The study design is very simple and consists initially of obtaining a dietary history, a
      blood sample, 24-hour urine collection and, subsequently, of determining the effects of a
      low-AGE diet for 4 months on the plasma levels of these compounds in a group of healthy
      subjects.
    

Detailed description: 
      Advancing age is known to be associated with increased oxidant stress (OS), increased
      prevalence of cardiovascular disease, impaired glucose tolerance, diabetes mellitus, decline
      of renal function, and accumulation of advanced glycation end products (AGEs). AGEs can lead
      to activation of transcriptional pathways, excessive proliferative/growth-related phenomena
      and sustained inflammation and through these different mechanisms may contribute
      significantly to the clinical complications of aging. Recently, it has become clear that a
      major source of AGE precursors and OS is the Western diet. The body turnover of AGEs involves
      specific receptors and is also dependent on renal function.

      While experimental work has linked AGE-mediated OS and chronic complications in aging
      animals, human studies are strikingly lacking. We plan to test the following two hypotheses:
      1) older men and women (age > 60 years) who consume standard diets (usually high in AGE
      content) will have higher serum levels of AGEs in conjunction with higher markers of OS,
      vascular dysfunction and inflammation when compared with younger subjects (age < 35 but >18
      years), and 2) dietary AGE restriction will reduce the serum levels of AGE, markers of OS,
      vascular dysfunction and inflammation and attenuate the difference between older and younger
      groups.

      Specific aims:

      To determine the effect of dietary AGE modification for 4 months on circulating levels of
      AGEs, markers of oxidative stress, vascular dysfunction, inflammatory mediators and
      AGE-receptor mechanisms in PBMN in old and young subjects. This will be a randomized study
      (Study 2).
    

Intervention name(s): Low AGE Diet; Regular Diet
Intervention type(s): Other; Other
Intervention description(s): Diet; Diet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Aging; oxidative stress; glycoxidative stress; glycation; inflammation; nutrition; low AGE intake; dietary AGEs