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Societies are progressively aging, with the oldest old (i.e., those aged >80-85 years) being the most rapidly expanding population segment. However, advanced aging comes at a price, as it is associated with an increased incidence of the so-called age-related conditions, including a greater risk for loss of functional independence. How to combat sarcopenia, frailty, and overall intrinsic capacity decline in the elderly is a major challenge for modern medicine, and exercise appears to be a potential solution. In this article, we first summarize the physiological mechanisms underlying the age-related deterioration in intrinsic capacity, particularly regarding those phenotypes related to functional decline. The main methods available for the physical assessment of the oldest old are then described, and finally the multisystem benefits that exercise (or "exercise mimetics" in those situations in which volitional exercise is not feasible) can provide to this population segment are reviewed. In summary, lifetime physical exercise can help to attenuate the loss of many of the properties affected by aging, especially when the latter is accompanied by an inactive lifestyle and benefits can also be obtained in frail individuals who start exercising at an advanced age. Multicomponent programs combining mainly aerobic and resistance training should be included in the oldest old, particularly during disuse situations such as hospitalization. However, evidence is still needed to support the effectiveness of passive physical strategies including neuromuscular electrical stimulation or vibration for the prevention of disuse-induced negative adaptations in those oldest old people who are unable to do physical exercise. © 2019 American Physiological Society. Compr Physiol 9:1281-1304, 2019., (Copyright © 2019 American Physiological Society. All rights reserved.)

Aims: To clarify the impact of Breslow's scores consisting of only lifestyle habits or American Heart Association's (AHA) Life's Simple 7 scores consisting of lifestyle habits and control targets on starting dialysis in people with or without diabetes mellitus (DM)., Methods: To pursue the study aims, we examined a nationwide database on 294,647 individuals with and without DM aged 19-72 y in Japan to pursue the study aims. Using multivariate Cox modeling, we evaluated and compared 5 risk factors based on the unfavorable lifestyle factors in Breslow's scores and the unfavorable lifestyle factors and clinical values in AHA Life's Simple 7 scores., Results: DM increased the risk of the initiation of dialysis 5- to sixfold but that risk did not increase with worsening of Breslow risk factors. Compared with no risk factor, 5 risk factors derived from AHA's Life's Simple 7 presented 9.8-fold and 4.2-fold risks for the initiation of dialysis in non-DM and DM, respectively. In comparison with non-DM and no risk factor, risk of the initiation of dialysis dramatically increased up to 32.3 times according to the number of AHA risk factors in those with DM., Conclusions: DM and risk factors derived from AHA's Life's Simple 7 synergistically increased the risk of the initiation of dialysis. Factors similar to those used to predict cardiovascular disease would also be useful to predict the initiation of dialysis. These approaches might be helpful in clinical practice and patient education., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00739-0., Competing Interests: Conflict of interestAuthor Hirohito Sone received research funding and research grant from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. and Novartis Pharma K.K. Author Taeko Osawa, Author Kazuya Fujihara, Author Mayuko Harada Yamada, Author Yuta Yaguchi, Author Takaaki Sato, Author Masaru Kitazawa, Author Yasuhiro Matsubayashi, Author Takaho Yamada, and Author Satoru Kodama declare that they have no conflict of interest., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aims: To determine the associations between combined urinary protein (UP) and a reduced estimated glomerular filtration rate (eGFR) and the risk of starting dialysis with or without diabetes mellitus (DM)., Methods: A nationwide database with claims data on 335,778 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of the severities of UP and eGFR on starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severities of UP and eGFR to predict the initiation of dialysis with and without DM., Results: Both eGFR < 60 and UP(+) were independent predictors for starting dialysis with and without DM, and their values exhibited a synergistic risk of dialysis. eGFR < 60 presented a nearly twofold risk for starting dialysis compared to UP(+) regardless of DM. Risk of starting dialysis was increased with UP(+) and eGFR ≥ 60 accompanied by DM although this association was not observed without DM. Those who had UP(-) and eGFR < 60 had a high risk of starting dialysis regardless of DM. Compared with DM(-)UP(-)eGFR ≥ 60, HRs for starting dialysis for DM(+)UP(+)eGFR ≥ 60, DM(+)UP(-)eGFR < 60 and DM(+)UP(+)eGFR < 60 significantly increased 17.7 (10.6-29.7), 25.5 (13.8-47.1) and 358.1 (239.1-536.5) times, respectively., Conclusions: eGFR < 60 and UP(+) together presented an extremely high risk of dialysis especially with DM. UP( +) increased the risk of starting dialysis regardless of the eGFR with DM. Both patient education and a treatment strategy by physicians might be helpful to avoid the progression of renal failure., Competing Interests: Conflict of interestAuthor Hirohito Sone received research funding and research grant from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. and Novartis Pharma K.K. Authors Taeko Osawa, Kazuya Fujihara, Mayuko Harada Yamada, Yuta Yaguchi, Takaaki Sato, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, and Satoru Kodama declare that they have no conflict of interest., (© The Japan Diabetes Society 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)