| Nowadays, aging population in human society, loosely defined as the people whoare65and over, is increasing in developed countries including USA, Japan andWestern Europe and even in developing countries like China. Aging populationunavoidably faces the challenges associated with increased age such as physiologicaldecline and greater incidence of age-related diseases such as cancer, Alzheimer’sdisease, osteoporosis, cataracts and type2diabetes. Understanding the biology ofaging keeps as an intriguing research topic and has become one of the major scientificchallenges in the quest to prevent and cure age-associated diseases, retard agingprocess and prolong lifespan. Aging research has experienced an unprecedentedadvance over recent years, particularly with the discovery that the rate of aging iscontrolled, at least to some extent, by genetic pathways and biochemical processesconserved in evolution. Recent Review enumerates nine tentative hallmarks thatrepresent common denominators of aging in different organisms, with specialemphasis on mammalian aging. These hallmarks are: genomic instability, telomereattrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing,mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and alteredintercellular communication. The determinants of lifespan are various and complex.Two different mechanisms are considered to be the primary cause of aging.Cumulative molecular damage caused by reactive oxygen species (ROS), theby-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by insulin and insulin-like growth factor1(IGF-1)signaling (IIS) pathway is the second mechanism (IIS concept).Temperature reduction (TR) is known to modulate aging and prolong lifespan ina variety of organisms, such as worms, fruit flies and fish, but the mechanisms remainlargely unknown. Our aging research is commenced on the annual fishNothobranchius guentheri (N.guentheri), one of the earliest fish models for agingresearch. We selected9-month-old males reared at26±1oC and followed by1monthculture at low temperature (22±1oC). Daily observation and record are taken on theirdevelopment and survival of two different temperature processing group. Here weclearly demonstrate that late onset TR from26oC to22oC prolongs5.2weeks of themean lifespan and3weeks of the maximum lifespan in the annual fish N.guentheri.We also show that late onset TR has a significant effect on the normal aging ofN.guentheri, which is able to decrease the accumulation of histological aging markersSA-β-Gal (senescence-associated β-galactosidase) in the epithelium and LF(Lipofuscin) in the liver, and to reduce the protein oxidation and lipid peroxidationlevels in the muscle. Moreover, we show that TR can enhance the activitiesantioxidase such as of CAT (catalase), GPX (glutathione peroxidase) and SOD(superoxide dismutase).To determine if late onset low temperature affects expression profiles ofrepresentative genes involved in cellular metabolism, gene regulation and heat shockresponse, qRT-PCR (Real-time Quantity PCR) and Western blot was performed. Ourdatum shows that late onset temperature reduction can slow down reduction of sirt1(silencing information regulator1) and foxO (forkhead box O). Interestingly, theexpression levels of hsp70(heat shock protein70) and hsf-1(heat shock transcriptionfactor1) showed no significant difference under any of the ambient temperaturestested.Taken together, our findings suggest that late onset TR, a simple non-intrusionintervention, can retard aging process in aged fish, resulting in their lifespan extension, via a combined action of antioxidant system and IIS pathway, providing a support toboth ROS concept and IIS concept. Furthermore, our study may help us to understandhow adaptation to certain cellular stresses, including nutrient availability, maymodulate mammalian lifespan and contribute to providing more comprehensive viewof anti-aging process. |
PDF Full Text Request