An aging Interventions Testing Program: study design and interim report

  title={An aging Interventions Testing Program: study design and interim report},
  author={Richard A. Miller and David E Harrison and Clinton M. Astle and Robert A. Floyd and Kevin Flurkey and Kenneth L. Hensley and Martin A. Javors and Christiaan Leeuwenburgh and James F. Nelson and Ennio Ongini and Nancy L. Nadon and Huber R. Warner and Randy Strong},
  journal={Aging Cell},
The National Institute on Aging's Interventions Testing Program (ITP) has developed a plan to evaluate agents that are considered plausible candidates for delaying rates of aging. Key features include: (i) use of genetically heterogeneous mice (a standardized four‐way cross), (ii) replication at three test sites (the Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT), (iii) sufficient statistical power to detect 10% changes in lifespan, (iv) tests for age… 

Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice

Blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of ND GA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism, and further studies are warranted to find whether NDGA, over a range of doses, might prove to postpone death and various age‐related outcomes reproducibly in mice.

Longitudinal Functional Study of Murine Aging: A Resource for Future Study Designs

Benzoxazole, which extends the lifespan of Caenorhabditis elegans, slowed age‐related femoral bone loss in mice and an online application was created that enables power and variance to be calculated for many clinically important metrics of aging with an emphasis on bone.

Design of aging intervention studies: the NIA interventions testing program

The development of an aging interventions testing program funded by the National Institute on Aging is described to test candidate interventions in a model system to highlight the challenges of long-term intervention studies and provides approaches to cope with the stringent requirements of a multi-site testing program.

Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels

The hypothesis that the IGF1 pathway plays a key role in regulating longevity in mice and indicates that common genetic mechanisms may exist for regulating IGF1 levels and lifespan is supported.

Lifespan extension drug interventions affect adipose tissue inflammation in aging.

The data suggest rapamycin may achieve lifespan extension in part through adipose tissue inflammation, and HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-α estradiol do not strongly alter these phenotypes-suggesting that acarbOSE and17- αEstradiol may not influence lifespan through mechanisms involving adipose tissues inflammation.

Accelerated failure time models provide a useful statistical framework for aging research

Identifying the Critical Gaps in Research on Sex Differences in Metabolism Across the Life Span

The goal of this article is to discuss the current state of research addressing sex differences in cardiometabolic health across the life span, to outline critical research gaps that must be addressed in response to NIH mandates, and to develop strategies to address sex as a biological variable to understand disease mechanisms as well as develop diagnostic and therapeutic modalities.

Aging, Disease, and Longevity in Mice

There is now substantial evidence, in some cases compelling and in others fairly preliminary, that mouse lifespan can be extended by 3 dietary interventions, by mutations in numerous genes, and by multiple drugs including rapamycin.

Development of clinical trials to extend healthy lifespan

Development of large-scale clinical trials designed to determine whether multiple age-related health conditions can be simultaneously alleviated with interventions targeting the underlying biology of aging are described.



Program for testing biological interventions to promote healthy aging

Statistical methods for testing effects on “maximum lifespan”

Body weight, hormones and T cell subsets as predictors of life span in genetically heterogeneous mice

In search of Methuselah: estimating the upper limits to human longevity.

Results indicate that in order for life expectancy at birth to increase from present levels to what has been referred to as the average biological limit to life (age 85), mortality rates from all causes of death would need to decline at all ages by 55%, and at ages 50 and over by 60%.

In pursuit of the longevity dividend

It is suggested that a concerted effort to slow aging begin immediately - because it will save and extend lives, improve health, and create wealth.

Exotic mice as models for aging research: polemic and prospectus.

Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly.

Quantitative trait loci for insulin-like growth factor I, leptin, thyroxine, and corticosterone in genetically heterogeneous mice.

The results show that the genetic controls over late-life hormone levels are complex and dependent on effects of genes that act both early and late in the life course.

Exercise increases average longevity of female rats despite increased food intake and no growth retardation.

Results show that exercise improves average longevity of rats independent of decreased availability of energy for cell proliferation and growth, and provide evidence that an increase in food intake is not harmful when balanced by a increase in energy expenditure.

Putative role of neuronal 5‐lipoxygenase in an aging brain

  • H. ManevT. UzK. SugayaT. Qu
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2000
The 5‐LOX pathway could become a promising target of neuroprotective therapies for the aging brain and putative role of neuronal 5‐lipoxygenase in an aging brain is proposed.