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首页> 美国卫生研究院文献>The Journal of Physiology >Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity
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Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity

机译：生理生理科学：靶向功能可延长健康寿命并达到最佳寿命

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Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio‐economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been ‘compression of morbidity’ and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, ‘geroscience’, is focused on healthspan extension. Superimposed on this background are new attitudes and demand for ‘optimal longevity’ – living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first‐line function‐preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel ‘nutraceutical’ compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio‐economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health.
机译：世界上大多数国家正经历着迅速而戏剧性的人口老龄化，这给个人，家庭，政府和社会带来了巨大的社会经济挑战以及机遇。减少人口老龄化对健康的影响的主要生物医学策略是“发病率压缩”，最近又增加了健康寿命，这两种方法都旨在延长健康的生命周期，并将慢性病和残疾的发展推迟到生命尽头的短暂时期。的确，最近在生物衰老研究领域建立的“ geroscience”领域专注于健康跨度的延长。在这种背景下叠加了对“最佳寿命”的新态度和新要求-寿命长，但身体健康，生活质量高。实现最佳寿命的关键障碍是随着年龄增长而发生的生理功能的逐渐下降，这会导致功能限制（例如，行动不便）并增加慢性病，残疾和死亡的风险。当前增加健康跨度的努力集中在减缓衰老的基本生物学过程，例如炎症/氧化应激，衰老增加，线粒体功能障碍，蛋白稳态受损和抗逆性降低。我们建议，在整个生命周期中优化生理功能应该是解决全球老龄化问题的任何当代生物医学政策的主要重点。有效的策略应随着年龄的增长而延迟，降低其功能或取消其功能降低（一级预防）和/或改善功能或已经减慢功能已受损的老年人的进一步衰退（二级预防）。具有规律的体育锻炼和理想的能量摄入/饮食组成的健康生活方式实践代表着保持一线功能的策略，包括现有和新药物以及新颖的“营养”化合物在内的药理作用是潜在的补充方法。未来的研究工作应着重于随着年龄的增长确定功能下降的时间模式，确定涉及的潜在机制和调节因子，并建立最有效的生活方式和维持功能的药理学选择。不断开发有效的行为方法以增强不同人群对健康老龄化行为的依从性，并持续分析扩大健康跨度的社会经济成本和收益将是重要的支持目标。为了满足人口老龄化带来的需求，需要对生理学进行新的重视，这需要研究人员在从基础科学到公共卫生的整个转化研究领域中进行合作，跨学科的努力。

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