再生医療から見た老化制御～幹細胞老化と老化組織との関係性から～

Aging and Bio-motor function. Stem cell aging and the implications for stem cell-based therapies for aging-related diseases and aged tissues.

　成体幹細胞は多くの組織に存在しており，正常組織の恒常性維持と修復に必須である。個体の老化に伴って，幹細胞の数の減少と機能低下が見られる。これは，個体老化が幹細胞の機能低下を引き起こしているのか，幹細胞の機能低下が個体老化の原因なのかははっきりしていない。 　本稿では，幹細胞自身に由来する老化変化のみならず，幹細胞を取り囲み，その機能を制御する微小環境と全身性因子からの幹細胞老化誘導モデルについて概説する。また，幹細胞移植により老化組織の機能改善を試みる際には，移植する幹細胞の種類により注意点が異なること，さらにレシピエントの老化組織からも移植後の幹細胞が影響を受ける可能性があることを述べる。

　Adult stem cells exist in most mammalian tissues to maintain their homeostasis and help repair them. Reductions in adult stem cell function and/or number are clearly associated with aging, however, the causal correlations between such findings and the effects of aging are largely unknown. Some stem cell functional changes, such as the loss of lineage specificity and self-renewal capacity, senescence and transformation, arise in stem cells autonomously during the aging process. These autonomous changes of stem cell functions reflect the damaging effects of age on the genome, epigenome, and proteome. Other stem cell functional changes are influenced by the age-related changes in the local microenvironments（niches）or systemic environments. If stem cell-based therapy can be used not only for age-related degenerative diseases, but also normal functional declines associated with aging, consideration of the behavior of stem cells based on effects from the local microenvironments（niches）and systemic environments in older individuals will therefore be needed.