Prevention of Neuromusculoskeletal Frailty in Slow-Aging Ames Dwarf Mice: Longitudinal Investigation of Interaction of Longevity Genes and Caloric Restriction

Ames dwarf (Prop1df/df) mice are remarkably long-lived and exhibit many characteristics of delayed aging and extended healthspan. Caloric restriction (CR) has similar effects on healthspan and lifespan, and causes an extension of longevity in Ames dwarf mice. Our study objective was to determine whether Ames dwarfism or CR influence neuromusculoskeletal function in middle-aged (82 ± 12 weeks old) or old (128 ± 14 w.o.) mice. At the examined ages, strength was improved by dwarfism, CR, and dwarfism plus CR in male mice; balance/ motor coordination was improved by CR in old animals and in middle-aged females; and agility/ motor coordination was improved by a combination of dwarfism and CR in both genders of middle-aged mice and in old females. Therefore, extension of longevity by congenital hypopituitarism is associated with improved maintenance of the examined measures of strength, agility, and motor coordination, key elements of frailty during human aging, into advanced age. This study serves as a particularly important example of knowledge related to addressing aging-associated diseases and disorders that results from studies in long-lived mammals.

Ames侏儒（Prop1df/df）小鼠寿命显著延长，且展现出诸多衰老延缓与健康寿命延长的特征。热量限制（Caloric restriction, CR）对健康寿命与寿命具有相似的积极影响，还可进一步延长Ames侏儒小鼠的寿命。本研究旨在探究Ames侏儒症或热量限制是否会对中年（82±12周龄）或老年（128±14周龄）小鼠的神经肌肉骨骼功能产生影响。在受试年龄组中，侏儒症、热量限制以及二者联合干预均可改善雄性小鼠的肌肉力量；平衡能力与运动协调能力可通过热量限制在老年小鼠及中年雌性小鼠中得到改善；而敏捷性与运动协调能力则可通过侏儒症联合热量限制，在两种性别的中年小鼠以及老年雌性小鼠中得到提升。因此，由先天性垂体功能减退所延长的寿命，与本次检测的肌肉力量、敏捷性及运动协调能力（人类衰老过程中衰弱的关键衡量指标）在高龄阶段的维持改善密切相关。本研究可为通过长寿哺乳动物研究获取的、与衰老相关疾病及病症干预相关的认知，提供极具重要性的参考范例。