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Kraken
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This study proved that controlling time-of-feeding can override the anti-longevity effect of caloric intake and is sufficient for lifespan extension [88].
Caloric restriction, limiting calorie intake without causing malnutrition, has been shown to extend lifespan in multiple model systems (de Magalhaes et al. 2012; Masoro 2005; Spindler 2010). When comparing mortality curve trajectories under CR or reduced T b, however, some studies have observed a difference between the two. Evidence of this comes from Drosophila whereby CR initially delays age-related mortality in the short-term, which results in an increase in the overall lifespan, although in the long-term the rate of the mortality trajectory is the same as that of non-CR flies (Fig. 2) (Mair et al. 2003). However, a lowered T b has a different effect whereby it extends lifespan as well as reducing the slope of the mortality trajectory (Fig. 2) (Miquel et al. 1976), suggesting that in Drosophila lowered T b and CR utilize alternative pathways to reduce mortality. Whether this is the case in homeotherms is unknown.
B6 (lymphoma prone) mice kept at a higher room temperature (30 °C) did not reduce T b when under CR and this caused a reduction in daily hypothermia and reduced the life-extending effects of CR and in particular its anti-lymphoma action (Koizumi et al. 1996). Likewise, CR is known to reduce cell proliferation and at higher room temperatures this effect weakens. It has therefore been suggested that CR’s induction of hypothermia could cause this anti-lymphoma action which promotes longevity. However, in MRL (autoimmune prone) mice the high room temperature (30 °C) had no effect in reducing the CR-mediated delay of autoimmune diseases (Koizumi et al. 1996).
Similarly, in fruit flies, changing back and forth the ambient temperature from hot to cold, animals have a similar longevity of flies kept in cold conditions (Liu and Walford 1972; Rikke and Johnson 2004), which suggest that it is not the exposure time to cold but rather physiological adaptations to it that are important.
Our analyses reveal a common network of genes under convergent evolution, encompassing established aging regulators such as insulin signaling, yet also identify flavonoid (aryl-hydrocarbon) metabolism as a pathway modulating longevity. The selective pressures on these pathways indicate the ancestral state of rockfishes was long lived and that the changes in short-lived lineages are adaptive. These pathways were also used to explore genome-wide association studies of human longevity, identifying the aryl-hydrocarbon metabolism pathway to be significantly associated with human survival to the 99th percentile. This evolutionary intersection defines and cross-validates a previously unappreciated genetic architecture that associates with the evolution of longevity across vertebrates.
Nevertheless, over-expression of telomerase increases the chances of cancer. If telomeres stay in repair, there is a greater chance of longevity, but there is also more cell division and a greater chance of mutation, which could result in cancer. Therefore, a long-lived cell is just a time bomb. Enhancing telomerase activity is, therefore, not a solution; it only allows the cells to live longer.
“Of note, PE26, PE39, PE42, PE59, PE68, PE78 and PE83 can prolong yeast CLS even under CR conditions, when all cellular processes that limit longevity under non-CR conditions are likely to be suppressed.”
PE26, PE39, PE42, PE59, PE68, PE78 and PE83 are from berries of Serenoa repens, aerial parts of Hypericum perforatum, leaves of Ilex paraguariensis, the whole plant of Solidago virgaurea, from the whole plant of Humulus lupulus, from root barks of Berberis vulgaris, from the whole plant of of Ilex paraguariensis, respectively.
“AMPK, a crucial cellular energy sensor, is activated by increases in the cellular AMP:ATP ratio. It has been shown that activation of AMPK via genetic or pharmacological intervention extends the lifespan of C. elegans and mice [36-39]. Since impaired mitochondrial respiration decreases ATP and therefore increases the AMP:ATP ratio, it is possible that AMPK plays a role in the long lifespan of mitochondrial respiration mutants.”
(Related to above quote) “As a cellular energy sensor, AMP-activated protein kinase (AMPK) is activated in response to a variety of conditions that deplete cellular energy levels, such as nutrient starvation (especially glucose), hypoxia and exposure to toxins that inhibit the mitochondrial respiratory chain complex.1, 2”
