INTRODUCTION Although aging has often been thought of as some intrinsic, immutable process, an alternative is to approach aging as a toxic endpoint resulting from a combination of endogenous and exogenous damage. Agin...INTRODUCTION Although aging has often been thought of as some intrinsic, immutable process, an alternative is to approach aging as a toxic endpoint resulting from a combination of endogenous and exogenous damage. Aging is then defined as consisting of a combination of functional declines observed in every organism system, occurring at different ages for different systems (Shock, 1985). One measure of this decline is death, and mortality is often used as a surrogate for aging. The sources of endogenous展开更多
Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) ma...Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) many variables that are related to the modulation of metabolic output vary dramatically at different times of the day; (2) various experimental variable and treatment groups must be synchronized with environmental cues that control circadian rhythms; and (3) multiple circadian variables may interact together to modulate the rate of aging. The rhythm for physiological factors such as whole animal metabolic output, body temperature, heart rate, urine flow, potassium, etc. were found to be dissociated or altered by the senescence process; behavioral variables such as spontaneous activity, wheel running, feeding and drinking, verbal performance, as well as sleep-wakefulness rhythms, seem to be accurate predictors of biological age. Circadian rhythms for a variety of enzymes of intermediary metabolism which are directly associated with energy metabolism have been well documented. These well-defined rhythms of enzyme activity have also been shown to degenerate with aging. Rhythms tend to lose amplitude as activity falls with age and as a general loss of regulation (especially time of day where maximal activity might be found) of activity across the 24-h span occurs. As with behavioral variables, changes in enzyme rhythms appear to accurately predict aging. Generally speaking, the loss of temporal organization with age, characterized by decreased circadian amplitude, loose internal synchronization, and poor response to external environmental time queues, is associated with poor health states and decreased longevity. Temporal rhythms for whole animal parameters are highly correlated with molecular events, such as regulation of cellular metabolism. DNA repair, and gene expression. Automated data acquisition and process control systems will be required for future Chronobiological studies to develop biomarkers of aging.展开更多
Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting a...Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important 'neurobehavioral' markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.展开更多
文摘INTRODUCTION Although aging has often been thought of as some intrinsic, immutable process, an alternative is to approach aging as a toxic endpoint resulting from a combination of endogenous and exogenous damage. Aging is then defined as consisting of a combination of functional declines observed in every organism system, occurring at different ages for different systems (Shock, 1985). One measure of this decline is death, and mortality is often used as a surrogate for aging. The sources of endogenous
文摘Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) many variables that are related to the modulation of metabolic output vary dramatically at different times of the day; (2) various experimental variable and treatment groups must be synchronized with environmental cues that control circadian rhythms; and (3) multiple circadian variables may interact together to modulate the rate of aging. The rhythm for physiological factors such as whole animal metabolic output, body temperature, heart rate, urine flow, potassium, etc. were found to be dissociated or altered by the senescence process; behavioral variables such as spontaneous activity, wheel running, feeding and drinking, verbal performance, as well as sleep-wakefulness rhythms, seem to be accurate predictors of biological age. Circadian rhythms for a variety of enzymes of intermediary metabolism which are directly associated with energy metabolism have been well documented. These well-defined rhythms of enzyme activity have also been shown to degenerate with aging. Rhythms tend to lose amplitude as activity falls with age and as a general loss of regulation (especially time of day where maximal activity might be found) of activity across the 24-h span occurs. As with behavioral variables, changes in enzyme rhythms appear to accurately predict aging. Generally speaking, the loss of temporal organization with age, characterized by decreased circadian amplitude, loose internal synchronization, and poor response to external environmental time queues, is associated with poor health states and decreased longevity. Temporal rhythms for whole animal parameters are highly correlated with molecular events, such as regulation of cellular metabolism. DNA repair, and gene expression. Automated data acquisition and process control systems will be required for future Chronobiological studies to develop biomarkers of aging.
文摘Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important 'neurobehavioral' markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.
