השעון היממתי (צירקדי) בהזדקנות: לקחים מעכברים מאריכי-ימים

Biological clocks are systems generating periodic oscillations in living cells independently of external ques. The circadian clock generates cycles of about (‘circa’) - but not exactly - 24 h (‘diem’). Hence, the phase of these oscillators must be corrected by a few minutes every day to synchronize with the geophysical time. This synchronization is controlled by light inputs in all light-sensitive organisms. In mammals, light signals are transmitted through the brain to the periphery in a complex hierarchical manner. The molecular core of the circadian oscillator, first discovered in flies, is a transcription-translation negative feedback loop. This mechanism is evolutionarily conserved, and is shared by most cells in multicellular organisms. In mammals, most physiology is influenced by the circadian timing, including metabolism, rest-activity rhythms, heart rate, blood pressure, etc. Circadian rhythm disruption has been implicated in shift work morbidity, jet lag, and malignancies. Aging can alter the amplitude or phase of circadian rhythms. It is not yet clear whether the circadian clock can causally determine longevity.

αMUPA mice constitute a unique transgenic model, displaying a beneficial circadian clock alongside increased health and life span (~15%). Compared to their wild type (WT) control mice, young MUPA mice exhibited high-amplitude circadian rhythms in several activities. αMUPA mice also showed spontaneously a 24 h period, a duration correlated with longevity in a large group of animal species. The 24 h αMUPA period was virtually life long, whereas that of WT was increased in aged mice. Furthermore, aged WT mice exhibited a 4-6 h shift in circadian food intake compared to young mice, while aged αMUPA mice maintained the young phase of food intake. Thus, aged WT mice showed an expected circadian disruption whereas aged αMUPA mice maintained a youthful circadian behavior. These findings suggest that the superior αMUPA clock could be involved in causally determining health and longevity of αMUPA mice.