Life's timekeeper is a 'free-running' intracellular oscillator synchronised across all cells. It runs throughout life splitting lifespan into equal length phases. During the maturational period it controls the overall rate of progression whereas in the post-maturational period it controls the overall rate of ageing. This includes the rate of senescence and hence time to death. As such life's timekeeper equates maturational and post-maturational time, hence explains the tight correlation between these time periods that has existed throughout mammalian evolution.
It has been hypothesized that the deamidation of glutaminyl and asparaginyl residues serves as a molecular clock for many biological processes including protein turnover, development, and aging. At present, this hypothesis has passed some experimental tests which are necessary but not sufficient for its acceptance. The current state of evidence about deamidation as a molecular clock is discussed.
Aging can be slowed in laboratory rodents by low-calorie diets, and changes in single genes can extend mouse life span by 40 percent or more. Therefore, despite its surface complexity and effects on multiple cells and intercellular systems, aging in mammals might also be retarded by both genetic and nongenetic means. If human aging could be slowed pharmacologically to the extent now possible in rodents, the effect on healthy life expectancy would exceed that of abolishing cancer, cardiovascular disease, and adult-onset diabetes.
As the basis for the lifelong clock and as a primary cause of aging, a process of shortening of hypothetical perichromosomal DNA structures termed chronomeres is proposed in the CNS. The lifelong clock is regulated by the shortening of chronomere DNA in postmitotic neurons of the hypothalamus. Shortening of these DNA sequences occurs in humans on a monthly basis through a lunasensory system and is controlled by release of growth hormone discharged from the anterior pituitary directly into the hypothalamus via local blood vessels.
Aging is an inevitable process that is associated to loss of functional capacities in several body systems, like the cardiovascular, the skeletal muscle mass, the osteoarticular and the neuro-immune-endocrine systems. Changes appear due to interactions between genetic factors and way of life, such as diet and sedentary life style. This review shows evidence from the past twenty years concerning the importance of physical exercise to reduce the deleterious effects of aging, regarding the improvement in functional performance, the prevention of diseases and increased longevity.
Somatosensory event-related phase-ordered gamma oscillations (40-Hz) to electric painful standard stimuli under an odd-ball paradigm were analyzed in 13 high, 13 medium, and 12 low hypnotizable subjects during waking, hypnosis, and post-hypnosis conditions. During these conditions, subjects received a suggestion of Focused Analgesia to produce an obstructive hallucination of stimulus perception; a No-Analgesia treatment served as a control. After hypnosis, a post-hypnotic suggestion was given to draw waking subjects into a deep hypnosis with opened eyes.
AIMS: Adverse cardiovascular events in humans occur with a day/night pattern, presumably related to a daily pattern of behaviours or endogenous circadian rhythms in cardiovascular variables. Healthy humans possess a scale-invariant/fractal structure in heartbeat fluctuations that exhibits an endogenous circadian rhythm and changes towards the structure observed in cardiovascular disease at the circadian phase corresponding to the time of the broad peak of adverse cardiovascular events (at about 10 AM).
Proceedings of the National Academy of Sciences of the United States of America
Human motor control systems orchestrate complex scale-invariant patterns of activity over a wide range of time scales (minutes to hours). The neural mechanisms underlying scale-invariance are unknown in humans. In rats, the master circadian pacemaker [suprachiasmatic nucleus (SCN)] is crucially involved in scale-invariant activity fluctuations over multiple time scales from minutes to 24 h. Aging and Alzheimer's disease (AD) are associated with progressive dysfunction of the SCN.
Aging is associated with an earlier timing of circadian rhythms and a shorter phase angle between wake time and the timing of melatonin secretion or the core body temperature nadir. Light has a phase-dependent effect on the circadian pacemaker, and modifications of habitual light exposure in older people could contribute to a change in the timing of circadian rhythms or in the phase angle of entrainment.
Journal of Applied Physiology (Bethesda, Md.: 1985)
Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50,000-10,000 BC) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for optimal metabolic function.
