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Background <p>Environmental enrichment training may delay cognitive decline in mild cognitive impairment (MCI) by reducing telomere shortening, a cellular marker of aging. We investigated whether combined physical/cognitive training affects leukocyte telomere length (LTL) in the randomized trial “Train the Brain”.</p> Methods <p>LTL was assessed in 94 MCI (75.1 ± 5.1&#xa0;years) subjects and 37 non-MCI subjects (73.2 ± 4.6&#xa0;years). MCI patients were assigned to receive either 7&#xa0;months of training or standard care. After 7&#xa0;months, both groups were reassessed for changes in LTL and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Telomerase reverse transcriptase (hTERT) mRNA and telomeric repeat-containing RNA (TERRA) were also tested in 24 patients.</p> Results <p>MCI patients had shorter LTL than controls (<i>p =</i> 0.02), and short LTL was associated with a higher risk of MCI (OR<sub>adjusted</sub> = 2.6; 95%CI, 1.1–6.0; <i>p =</i> 0.03). Training improved ADAS-cog scores (T<sub>0</sub> = 15.1 ± 4.8 to T<sub>7</sub> = 13.4 ± 5.0, <i>p =</i> 0.01) and increased LTL (T<sub>0</sub> = 0.97 ± 0.21 to T<sub>7</sub> = 1.04 ± 0.23, <i>p =</i> 0.04). hTERT mRNA levels were negligible in MCI patients at T0 and T7, indicating inactive telomerase. TERRA expression increased in untrained MCI (<i>p =</i> 0.02), which may reflect impaired telomere homeostasis.</p> Conclusions <p>MCI patients have shorter telomeres, and combined training lengthens them, suggesting modifiable telomere homeostasis through non-pharmacological intervention. Telomere shortening may underlie increased telomeric transcription in untrained individuals, highlighting telomeric non-coding RNAs as potential therapeutic targets in age-related disease.</p>

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Combined physical and cognitive training enhances telomere length in mild cognitive impairment patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月31日

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  • Andrea Borghini,
  • Paola Canale,
  • Rosa Sicari,
  • Nicoletta Berardi,
  • Fabrizio d’Adda di Fagagna,
  • Alessandro Sale,
  • Maria Grazia Andreassi,
  • L. Maffei,
  • E. Picano,
  • A. Angelucci,
  • F. Baldacci,
  • L. Baroncelli,
  • T. Begenisic,
  • P. F. Bellinvia,
  • L. Biagi,
  • J. Bonaccorsi,
  • E. Bonanni,
  • U. Bonuccelli,
  • C. Braschi,
  • M. Broccardi,
  • R. M. Bruno,
  • M. Caleo,
  • C. Carlesi,
  • L. Carnicelli,
  • G. Cartoni,
  • L. Cecchetti,
  • M. C. Cenni,
  • R. Ceravolo,
  • L. Chico,
  • S. Cintoli,
  • G. Cioni,
  • M. Coscia,
  • M. Costa,
  • G. D’Angelo,
  • P. D’Ascanio,
  • M. De Nes,
  • S. Del Turco,
  • E. Di Coscio,
  • M. Di Galante,
  • N. di Lascio,
  • F. Faita,
  • I. Falorni,
  • U. Faraguna,
  • A. Fenu,
  • L. Fortunato,
  • R. Franco,
  • L. Gargani,
  • R. Gargiulo,
  • L. Ghiadoni,
  • F. S. Giorgi,
  • R. Iannarella,
  • C. Iofrida,
  • C. Kusmic,
  • F. Limongi,
  • M. Maestri,
  • M. Maffei,
  • S. Maggi,
  • M. Mainardi,
  • L. Mammana,
  • A. Marabotti,
  • V. Mariotti,
  • E. Melissari,
  • A. Mercuri,
  • S. Micera,
  • S. Molinaro,
  • R. Narducci,
  • T. Navarra,
  • M. Noale,
  • C. Pagni,
  • S. Palumbo,
  • R. Pasquariello,
  • S. Pellegrini,
  • P. Pietrini,
  • T. Pizzorusso,
  • A. Poli,
  • L. Pratali,
  • A. Retico,
  • E. Ricciardi,
  • G. Rota,
  • S. Sbrana,
  • G. Scabia,
  • M. Scali,
  • D. Scelfo,
  • G. Siciliano,
  • F. Stea,
  • S. Taddei,
  • G. Tognoni,
  • A. Tonacci,
  • M. Tosetti,
  • S. Turchi,
  • L. Volpi

摘要

Background

Environmental enrichment training may delay cognitive decline in mild cognitive impairment (MCI) by reducing telomere shortening, a cellular marker of aging. We investigated whether combined physical/cognitive training affects leukocyte telomere length (LTL) in the randomized trial “Train the Brain”.

Methods

LTL was assessed in 94 MCI (75.1 ± 5.1 years) subjects and 37 non-MCI subjects (73.2 ± 4.6 years). MCI patients were assigned to receive either 7 months of training or standard care. After 7 months, both groups were reassessed for changes in LTL and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Telomerase reverse transcriptase (hTERT) mRNA and telomeric repeat-containing RNA (TERRA) were also tested in 24 patients.

Results

MCI patients had shorter LTL than controls (p = 0.02), and short LTL was associated with a higher risk of MCI (ORadjusted = 2.6; 95%CI, 1.1–6.0; p = 0.03). Training improved ADAS-cog scores (T0 = 15.1 ± 4.8 to T7 = 13.4 ± 5.0, p = 0.01) and increased LTL (T0 = 0.97 ± 0.21 to T7 = 1.04 ± 0.23, p = 0.04). hTERT mRNA levels were negligible in MCI patients at T0 and T7, indicating inactive telomerase. TERRA expression increased in untrained MCI (p = 0.02), which may reflect impaired telomere homeostasis.

Conclusions

MCI patients have shorter telomeres, and combined training lengthens them, suggesting modifiable telomere homeostasis through non-pharmacological intervention. Telomere shortening may underlie increased telomeric transcription in untrained individuals, highlighting telomeric non-coding RNAs as potential therapeutic targets in age-related disease.