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Ageing as upregulation failure
1Department of Veterinary Pathology, University of Sydney, NSW, Australia.
Abstract:
This paper investigates similarities in physiological senescent changes in various mammalian organ systems and relates these to postulated mechanisms of age modulation. It proposes that the observed decline in homeostasis with age is due to an inability of target cells, of neural, endocrine and other forms of control, to upregulate after their downregulation. The well-documented flattening of circadian rhythms with age, particularly the loss of the sustained diurnal hypothermic phase, is described as integral to such change, and maintenance or induction of certain youthful circadian patterns is proposed as a means of restoring homeostasis in senescence and other conditions.
Insights
Aging causes physiological decline due to cellular inability to upregulate, impacting homeostasis. Restoring youthful circadian rhythms may help reverse this aging process and improve health.
Area of Science:
- Gerontology
- Physiology
- Chronobiology
Background:
- Physiological changes occur across mammalian organ systems during senescence.
- Age-related decline in homeostasis is a key characteristic of aging.
- Circadian rhythms flatten with age, notably the loss of the diurnal hypothermic phase.
Purpose of the Study:
- To investigate similarities in physiological senescent changes across mammalian organ systems.
- To relate these changes to proposed mechanisms of age modulation.
- To explore the role of circadian rhythms in aging and homeostasis.
Main Methods:
- Comparative analysis of physiological senescent changes in various mammalian organ systems.
- Review of postulated mechanisms of age modulation.
- Examination of age-related alterations in circadian rhythms and homeostasis.
Main Results:
- Identified common physiological senescent changes across different mammalian organ systems.
- Proposed that cellular inability to upregulate after downregulation contributes to age-related homeostasis decline.
- Linked the flattening of circadian rhythms, including loss of diurnal hypothermia, to senescence.
Conclusions:
- Cellular regulatory dysfunction is central to age-related homeostasis loss.
- Restoring youthful circadian patterns, like sustained diurnal hypothermia, may be a strategy to improve homeostasis in aging.
- This approach could offer new avenues for interventions in senescence and related conditions.