Laboratory of Molecular Medicine and Biotechnologies, IRCCS Fondazione Don Carlo Gnocchi ONLUS, Piazza Morandi 3, 20100, Milan, Italy.
Geriatic Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
J Transl Med. 2023 Feb 2;21(1):67. doi: 10.1186/s12967-023-03911-3.
Frailty, defined as physical performance impairment, is a common condition in older adults and can anticipate the development of sarcopenia, a geriatric syndrome characterized by loss of muscle strength and mass. microRNAs (miRNAs) are short molecules of RNA endowed with the ability to modulate gene expression; miRNAs are present in serum and are considered potential biomarkers for several diseases. Serum concentration of miR-451a, miR-93-5p, miR-155-5p, miR-421-3p, miR-425-5p, miR-495-3p and miR-744-5p was recently shown to be altered in sarcopenic patients.
We verified if a particular miRNAs pattern could be detected in frailty as well by analyzing these molecules in 50 frail and 136 robust subjects. Additionally, a subgroup of these subjects (15 frail and 30 robust) underwent a 12-week program based on a multicomponent exercise protocol (VIVIFRAIL) consisting of resistance training, gait retraining, and balance training. After the program, serum miRNAs concentration was measured again, to verify whether the physical activity had an effect on their concentration. Moreover, clinical characteristics and indicators of physical performance of all subjects were compared before and after intervention to verify the effect of the VIVIFRAIL program.
At the end of the multicomponent exercise program, Short Physical Performance Battery (SPPB) score as well right and left handgrip (p < 0.05) were significantly increased in frail subjects; right and left handgrip significantly were increased also in robust subjects (p < 0.05). Interestingly, the variation of SPPB was significantly higher in frail compared to robust subjects (p < 0.0001). Moreover, at the end of the program, in frail compared to robust subjects: miR-451a serum concentration was significantly increased (frail: 6.59 × 10; 1.12 × 10-2.5 × 10 c/ng; robust: 2.31 × 10; 1.94 × 10-2.01 × 10 c/ng) (p < 0.05); and 2) miR-93-5p and miR-495-3p serum concentration was reduced, whereas that of miR-155-5p was significantly increased (p < 0.05 in both cases). Serum concentration of miR-93-5p and miR-495-3p was decreased, and that of miR-155-5p was increased at the end of the program in robust subjects alone, statistical significance being reached for miR-93-5p alone (p = 0.02).
These results suggest that serum miR-451a should be investigated as a potential biomarker for frailty and show that the VIVIFRAIL multicomponent program modulates circulatory miRNAs expression, at least in older adults.
衰弱是一种常见的老年病,其定义为身体机能障碍,可以预测肌肉减少症的发生,肌肉减少症是一种以肌肉力量和质量丧失为特征的老年综合征。微小 RNA(miRNA)是一种具有调节基因表达能力的短链 RNA,存在于血清中,被认为是多种疾病的潜在生物标志物。最近研究表明,肌少症患者的血清 miR-451a、miR-93-5p、miR-155-5p、miR-421-3p、miR-425-5p、miR-495-3p 和 miR-744-5p 浓度发生改变。
我们通过分析 50 名衰弱患者和 136 名健康患者的这些分子,验证了在衰弱患者中是否可以检测到特定的 miRNAs 模式。此外,这些患者中的一个亚组(15 名衰弱和 30 名健康)接受了基于多成分运动方案(VIVIFRAIL)的 12 周计划,该方案包括阻力训练、步态再训练和平衡训练。计划结束后,再次测量血清 miRNAs 浓度,以验证身体活动是否会影响其浓度。此外,还比较了所有受试者干预前后的临床特征和身体表现指标,以验证 VIVIFRAIL 方案的效果。
多成分运动计划结束时,衰弱受试者的短体适能测试(SPPB)评分以及右手和左手握力(p<0.05)均显著增加;健康受试者的右手和左手握力也显著增加(p<0.05)。有趣的是,衰弱患者的 SPPB 变化明显高于健康患者(p<0.0001)。此外,在计划结束时,与健康受试者相比,衰弱患者的血清 miR-451a 浓度显著增加(衰弱:6.59×10;1.12×10-2.5×10 c/ng;健康:2.31×10;1.94×10-2.01×10 c/ng)(p<0.05);并且 2)miR-93-5p 和 miR-495-3p 血清浓度降低,而 miR-155-5p 血清浓度显著增加(p<0.05)。在健康受试者中,miR-93-5p 和 miR-495-3p 血清浓度降低,miR-155-5p 血清浓度升高,miR-93-5p 血清浓度升高具有统计学意义(p=0.02)。
这些结果表明,血清 miR-451a 可作为衰弱的潜在生物标志物进行研究,并表明 VIVIFRAIL 多成分方案可调节循环 miRNA 的表达,至少在老年人中如此。