The effect of a restricted feeding regimen of different duration on behavior and the mTOR signaling pathway in the cortex and hippocampus of aging male and female Wistar rats

[M. Prvulović]

156 str.

Biologija - Neurobiologija, Animalna i humana fiziologija / Biology - Neurobiology, Animal and human physiology

Starenje je složen biološki proces praćen postepenim gubitkom fizoloških funkcija i promenama u strukturi i funkciji svih sistema, pa i nervnog. Kao jedna od najefikasnijih intervencija u produženju životnog veka i odlaganju starosno zavisnih promena se pokazala dijetalna restrikcija (DR), definisana kao smanjenje kalorijskog unosa bez pothranjenosti. Međutim, o uticaju koji ima starost organizma i dužina trajanja DR na korisne efekte po kojima je DR poznata, se malo zna. U ovoj studiji ispitan je uticaj 40% DR različitog trajanja i početka na promene telesne mase, preživljavanje, krhkost, ponašanje, ekspresiju dopaminskih receptora i mTOR signalizaciju kod mužjaka i ženki Wistar pacova. Kod 18-mesečnih ženki, DR je smanjila smrtnost, poboljšala memoriju i smanjila anksiozno ponašanje, bez obzira na to da li je započeta u ranom ili kasnom periodu života, dok je kod starih ženki efekat zavisio od trenutka otpočinjanja DR. Kod mužjaka, DR je povećala preživljavanje i smanjila krhkost, ali nije poboljšala memoriju, dok je anksioznost bila povećana u svim grupama. Ekspresija proteina mTOR signalnog puta se menjala u zavisnosti od pola, starosti organizma i dužune trajanja DR. Rezultati ističu ključnu ulogu pola i vremena otpočinjanja DR. Iako rezultati potvrđuju da je DR moćna strategija za zdravo starenje negativni efekti kasno započete DR naglašavaju važnost definisanja optimalnog vremenskog okvira za uvođenje DR, ukazujući na potrebu za personalizovanim pristupom u u intervencijama za odlaganje starosnih promena.

Aging is a complex biological process characterized by a gradual loss of physiological functions accompanied with changes in the structure and function of all systems, including the nervous system. Dietary restriction (DR), defined as a reduction in caloric intake without malnutrition, has proven to be one of the most effective interventions for extending lifespan and delaying age-related changes. However, data are lacking on how the onset and duration of DR, as well as sex, influence its beneficial effects. This study examined the effects of 40% DR of various duration and onset on body weight, survival, frailty, behavior, dopamine receptor expression, and mTOR signaling in male and female Wistar rats. In 18-month-old females, DR reduced mortality, improved memory, and decreased anxiety-related behavior, regardless of whether it was initiated early or late in life, while the effect in older females depended on the timing of when DR was initiated. In males, DR increased survival and reduced frailty, but did not improve memory, whereas anxiety was heightened in all groups. The expression of proteins in the mTOR signaling pathway varied depending on sex, age, and the duration of DR. The results highlight the critical roles of sex and the timing of DR initiation. Although the findings confirm that DR is a powerful strategy for healthy aging, the negative effects of late-started DR emphasize the importance of defining an optimal timeframe for implementing DR, indicating the need for a personalized approach in interventions aimed at delaying age-related changes.

Dijetalna restrikcija, starenje, krhkost, ponašanje, anksioznost, memorija, mTOR, dopaminski receptori

Dietary restriction, aging, frailty, behavior, anxiety, memory, mTOR, dopamine receptors

577.25:612.8(043.3)

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