Energy excess is the main cause of accelerated aging of mammals

Abstract

The analysis of cases of unusually high longevity of naked mole rats and an alternative explanation of the phenomenon of calorie restriction effects in monkeys allowed for postulating that any factor preventing an excess of energy consumed, leads to increased lifespan, both in evolutionary and an individual lifetime scale. It is postulated that in mammals the most destructive processes resulting in shortening of life are not restricted to the phenomena explained by the hyperfunction theory of Mikhail Blagosklonny. Hyperfunction, understood as unnecessary or even adverse syntheses of cell components, can be to some extent prevented by lowered intake of nutrients when body growth ceases. We postulate also the contribution of glyco/lipotoxicity to aging, resulting from the excess of energy. Besides two other factors seem to participate in aging. One of them is lack of telomerase activity in some somatic cells. The second factor concerns epigenetic phenomena. Excessive activity of epigenetic maintenance system probably turns off some crucial organismal functions. Another epigenetic factor playing important role could be the micro RNA system deciding on expression of numerous age-related diseases. However, low extrinsic mortality from predation is a conditio sine qua non of the expression of all longevity phenotypes in animals. Among all long-lived animals, naked mole rats are unique in the elimination of neoplasia, which is accompanied by delayed functional symptoms of senescence. The question whether simultaneous disappearance of neoplasia and delayed senescence is accidental or not remains open.

Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling

“…CR can prevent renal aging even in an old age CR, an effective way to prevent energy excess, 33 has been reported to extend lifespan in diverse species including yeast, nematodes, flies and mammals. 4,34 Encouraging results are also achieved in Rhesus Monkeys, the close relatives to humans, in which lower age-related deaths and retardant age-associated pathologies onset were observed with CR application.…”

Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster

“…Energy excess is the main cause of accelerated aging [ 55 ]. Limiting calorie intake may counteract the deleterious effects of aging [ 56 ].…”

Novel treatment strategies for chronic kidney disease: insights from the animal kingdom

“…[H2] Caloric restriction and ageing. Although dietary phosphate restriction is one mechanism to slow vascular calcification and ageing, a more effective approach to extend the lifespan of animals is by caloric restriction (147), which has demonstrated efficacy in both short-lived species, including flies, worms, rats, mice (148), and more long-lived species, such as primates (149). Fat stores, especially those generated during fructose metabolism, result in fructoseinduced oxidative stress, which is associated with increased translocation of NRF2 to the nucleus, decreases in mitochondrial DNA content and mitochondrial dysfunction, with subsequent cellular apoptosis (150,151).…”