Notice Number: NOT-AG-07-005
Release Date: February 2, 2007
National Institute on Aging (http://www.nia.nih.gov )
The National Institute on Aging is soliciting information from academic investigators as well as pharmaceutical companies, biotechnology firms, and other health research-oriented organizations, regarding needs for, experience with, and availability of animal models for research on issues related to the co-occurrence of conditions or diseases (“multiple morbidities”) commonly observed among older persons.
More than one half of persons age 65 years and older have multiple medical conditions. Importantly, many of these co-occurring conditions appear to have synergistic interactions resulting in functional decline, additional morbidities, and mortality greater than expected from additive models of disease interactions. Recent publications have emphasized the problems that arise when medical management approaches each of multiple morbidities as an individual disease process.
Understanding of the associations of co-occurring conditions and diseases with aging processes, the effects of one condition on risk for another, and the mechanisms by which interactions of co-occurring conditions and diseases contribute to poor functional and health outcomes, is critical to our ability to improve and optimize medical care for older patients. Unfortunately, much of the research needed to explore these interactions cannot be accomplished in the human clinical setting and thus requires animal models of co-occurring disease processes and aging.
To address these issues, the NIA is considering approaches to promote research in laboratory animal models of co-occurring conditions. It is recognized that many animal models only recapitulate limited aspects of a disease process. However, it is hoped that manipulating models under specific conditions might allow the study of specific aspects of co-morbidities in these models. As an initial step in the planning process, NIA is requesting relevant information from clinical researchers familiar with issues related to comorbidities in older persons, as well as basic scientists experienced in the use of animal models to study diseases, functional impairments, and/or aging mechanisms. Information is requested with regards to the existence of animal models that replicate more than one chronic age-related disease, or the possibility of adapting available models that address one specific disease, for usage as models of comorbidity. Models may be spontaneously arising coexisting conditions in existing animal aging models, or genetically engineered, natural mutations, diet- or surgically-induced, but they must address at least two independent morbidities, relevant to the human population.
Co-occurring conditions of interest include, but are not limited to age-related cardiovascular conditions (e.g., coronary heart disease, hypertension), metabolic conditions (e.g., diabetes, metabolic syndrome), conditions of the nervous system (cognitive decline, neurodegenerative and cerebrovascular diseases and motor and sensory abnormalities), musculoskeletal conditions (e.g., osteoarthritis, osteoporosis), age-related malignancies, and age-related infectious (e.g., pneumonia). Interactions of age-related physiologic impairments (e.g., in responses to stressors) and functional impairments (e.g., in physical performance) with each other and with other morbidities are also of interest. Research topics of interest include the role of aging processes in the development of multiple coexisting conditions, the role of one age-related condition in the development or clinical presentation of another age-related condition, and interactions of coexisting conditions (and their treatments) in old age, with regard to pathologic consequences and effects of treatment for one condition on another condition.
The focus of this request is not on the prevalence of these issues in human populations, but rather, the focus is on availability and possible interest/capability of development of models that can be used to study these comorbidities in animals. Animal models supported by ongoing NIH animal models programs, as well as other models and conditions, are of potential interest.
The NIA solicits information and general comments regarding the research areas described above. Specifically, we seek answers to any or all of the questions below. (Answers should be brief, and if possible, should include one or two references on comorbidities of special interest and/or suggested animal models.)
1. For which specific human age-related comorbidities are there particular needs for animal models to support avenues of research not feasible in human studies, and what research issues could be addressed by such models?
2. What, if any, existing animal models of co-occurring conditions are available to study interactions of age-related diseases and conditions and their mechanisms? Do these models include interactions with aging processes (i.e., were they created in older animals, or have younger animals with the co-occurring conditions been followed into advanced age)?
3. Which, if any, animal models of specific individual conditions and/or processes are well suited for combination with models of other conditions to address problems of comorbidity that are relevant to human conditions?
4. In which animal models of specific individual conditions, if any, has the development of additional conditions or complications with advancing age been characterized? For example, do the animals develop complications of the underlying disease process or other co-occurring conditions as they age?
5. For animal models of normal, accelerated or retarded aging, including both genetically and dietary manipulated models, to what extent have combinations of age-related conditions been characterized, and which models develop combinations of diseases commonly found in humans?
This request for information is for planning purposes only and shall not be construed as a solicitation for applications or as an obligation on the part of the government. The government will not pay for the preparation of any information submitted or for the government’s use of that information.
Please send comments (and include the Notice number AG-07- 005 in the subject line) to: Dr. Ying Tian at firstname.lastname@example.org by February 21, 2007. This description should be sent by electronic mail, either as an e-mail message or as an attachment in Word, Adobe or other widely used text format.
Acknowledgement of receipt of responses will not be made, nor will respondents be notified of the government’s assessment of the information received. No basis for claims against the government shall arise as a result of responses to this request for information, or in the government’s use of such information as either part of our evaluation process or in developing specifications for any subsequent announcement. Responses will be held in a confidential manner, but the general content of responses may be shared anonymously with the NIA National Advisory Council on Aging. Any proprietary information should be so marked.
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