Lifespan-extending Effect Research Articles

Longevity of exercising male rats: effect of an antioxidant supplemented diet

Food restriction increases maximal life span in rodents. Male rats that exercise in voluntary running wheels do not have an increase in maximal longevity despite a relative caloric deficit. In contrast, sedentary rats that are food restricted so as to cause the same caloric deficit have an extension of maximal longevity. It seemed possible that exercise-induced oxidative stress might prevent a maximum life span-extending effect of a caloric deficit to manifest itself. This study was done to determine if antioxidants would allow a maximal longevity-extending effect of exercise to manifest itself in male rats. The antioxidant diet had no effect on longevity of the runners (Antiox., 951±158 days versus control 937±171 days), or of the sedentary controls (875±127 versus 858±152 days). As in previous studies, wheel running modestly increased average longevity (≈9%), but had no effect on maximal life span. The finding that antioxidants had no effect on longevity of the wheel runners supports the interpretation that the caloric deficit induced by exercise in male rats does not have a life-extending effect that is countered by oxidative tissue damage.

Geroprotector efficiency depends on viability of control population: life span investigation in D. melanogaster

Ability of the radical spin trap 4-hydroxy-2,2,6,6,-tetramethyl-1-piperidine- N-oxyl (4-hydroxy-TemPO, (4HT)), to delay senescence in D. melanogaster has been studied. The spin trap, at a concentration of 0.2%, was added to the culture medium at the flies development stage. Reliable correlation ( r=0.76, P < 0.05) has been found between the viability of a control population, assessed by the mean life span (LS) value, and the level of LS alteration after geroprotector treatment in a corresponding experimental population. Thereby the local minimum values and local decreases in the mean LS in successive generations of the control line are associated most likely with LS extension effects in the corresponding experimental groups after 4HT treatment; and on the contrary, the local maximum values and local increases in the mean LS of the control line are associated more probably either with LS decreasing effects in the corresponding experimental groups or with the lack of significant differences between the control and experimental groups. A possible mechanism of the discovered phenomenon is discussed, based on the concept about free-radical activity variations. A probability approach to the evaluation of geroprotector efficiency in serial studies is proposed.

Differential response to UV stress and DNA damage during the yeast replicative life span.

The yeast Saccharomyces cerevisiae is mortal. Before they die, individual yeasts bud repeatedly producing a finite number of progeny, which have the capacity for a full life span. A feature of aging in many species is the waning of resistance to stress. To determine whether this is the case in yeast, we have examined the survival (viability) of age-synchronized populations of yeasts of various ages, spanning youth, midlife, and old age, after irradiation with ultraviolet light (UV). Resistance to UV was biphasic. There was an increase through midlife, followed by a precipitous decline. For comparison, another mutagenic agent, ethyl methanesulfonate (EMS), was tested in the same way. The response was very different. A uniphase decrease in resistance to this DNA-alkylating agent was found with a plateau later in life. The results argue that the increase in resistance to UV with age is an active process and not simply a monotonic age change. RAS2 is among the genes that determine yeast longevity. This gene is preferentially expressed in young cells and has a life span-extending effect on yeasts. One known function of RAS2 is to mount a protective response to irradiation by UV, which occurs independently of DNA damage. The distinction between UV and EMS found here is consistent with the notion that resistance to UV plays a role in yeast longevity in a manner not related to DNA damage. Furthermore, it suggests that RAS2 may participate in this response. We have found that RAS2 expression and UV resistance coincide in middle-aged yeasts bolstering this possibility. These data and the eclipse in activity of several longevity determining genes at midlife in yeasts also raise the possibility that active life maintenance processes function through this period, after which the organism operates on any remaining reserves until death.