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- Open Access
Hypothalamic involvement in premature aging laminopathies
Orphanet Journal of Rare Diseases volume 10, Article number: O6 (2015)
Caloric restriction (CR), the reduced intake of calories without malnutrition, extends lifespan of many organisms, from yeast to mammals, and delays the progression of age-related diseases. Evidence show that hypothalamus is a crucial brain region for the progress of whole-body aging and the beneficial effects induced by CR are regulated by nutrient-sensing neurons located in the hypothalamus. Although CR's beneficial effects in delaying human aging are promising, its application for long periods is very difficult to maintain and not feasible to apply to fragile children with progeria. To overcome this problem, the induction of protective endogenous mechanisms, or pharmacological agents, could theoretically be used to mimic the beneficial effects of CR without its discomfort. Our group showed that hypothalamus of Zmpste24-/- mouse has lower levels of Neuropeptide Y, comparing to wild-type animals. Moreover, they showed that targeting the Neuropeptide Y system in hypothalamus, as a CR mimetic strategy, delays or reverts some ageing features of Zmpste24-/- mice. Further studies are needed to confirm this innovative approach and if it could be translational to progeria children.
Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, et al: Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature. 2013, 497 (7448): 211-6.
Dacks PA, Moreno CL, Kim ES, Marcellino BK, Mobbs CV: Role of the hypothalamus in mediating protective effects of dietary restriction during aging. Frontiers in neuroendocrinology. 2013, 34 (2): 95-106.
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Cavadas, C. Hypothalamic involvement in premature aging laminopathies. Orphanet J Rare Dis 10, O6 (2015). https://doi.org/10.1186/1750-1172-10-S2-O6
- Public Health
- Beneficial Effect
- Brain Region
- Caloric Restriction
- Pharmacological Agent