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どうして生命は老化する?

傍観者さんのエントリ「不老不死は可能か?」(私たんニュース 経由)で、生体が不老不死になるためにはどんな用件が必要なのか、分子生物学的知見から述べられていて面白い。

不老不死のキーワードは主に二つ挙げられると思う。
「フリーラジカル」と「テロメア」だろう。
「フリーラジカル(活性酸素)」と「テロメア」に焦点を当てた議論。 確かにフリーラジカルによる細胞の損傷と、テロメアが短くなることによる細胞分裂の阻害は生命を維持する上で障害になることは間違いないが、これが老化の総合的な原因かというとそうではないようにも思われる。(最終的にはフリーラジカルやテロメアが効いてくるわけだが)

これは老化がひとつの要因で起こっているモノではなく、生命が総体として老化というイベントを起こしているという考え方である。 簡単に言うと誕生から時間が経過することで外的要因・内的要因によって生命を維持するシステムのバランスが崩れてくると云うことであろう。
財団法人東京都老人総合研究所に老化の原因について仮説として端的にまとめられている

仮説-1)プログラム説 (program theory of aging)
種の最長寿命は決まっている、また種にはそれぞれ固有の一般化できる老化形質が発現するという事実から派生した概念である。
私見としては、生殖年齢を過ぎて後に、それまでは極めて効果的に作用していた個体の恒常性(ホメオスタシス)維持機構(種固有のゲノム維持機構とほぼ同義)が崩壊するに伴い、老化形質が顕在化すると考えたい。即ち種毎に、内在的に、老化を促進する因子と抑制するあるいはゲノム崩壊を修復する因子が存在すると予想される(一部は既に発見されている)。しかし、一定時間にセットされた積極的自殺装置的機構が種の寿命を決定するというような、狭義のプログラム説は成立しないと考える。

仮説-2)エラー蓄積説・エラー破綻説 (error catastroph theory of aging)
最近明らかにされつつある事実はゲノムの修飾・改変が起こり遺伝子発現が変異したり、蛋白質の翻訳後の修飾により機能変化が起こる等の変異(エラー)が蓄積することにより、個体の生命維持の破綻に至るとの考えを支持している。

仮説-3)ゲノム総体として、生殖活動期間までの遺伝子修復を保証する機構は基本的にはすべての有性生殖する生物に備わるものと考える。種に特異的な(換言するとゲノムに規定された)その保証期間以降のエラー修復不全期間(老化期間)、不全状態の認識の仕方、さらには一定以上の異常は許容しない機構(一種の自殺機構ともいえる)が備わっている。

どの説も基本的には若い頃(生殖活動期間)には非常に優れたバランスの恒常性(ホメオスタシス)および遺伝子修復機能が働いており、老化として観測されるようなことが起こることを抑制しているという点で共通している。

この考え方は生殖活動が生命の目的であると考えれば(つまり個は種から見れば生殖さえすんでしまえばもういらなくなる)、非常に良くできた仕組み。 もちろんこの説を支持するとしても、なぜ生殖器官が限られているのかという疑問が沸いてくるのだが、その答えはまだ分子生物学的には明らかになっていないと思う。

最近、老化を司っている遺伝子WIRED NEWS)などの報告もある。 この遺伝子は飢餓状態に陥ったときに生体としての機能を低下させ、飢餓状態から脱出するまでの間必要最低限の生体活動レベルで維持しようとするシステムがあることを示している。 栄養的に乏しいと生殖活動そのものが困難なので、若さを保って生殖活動できる時期を淡々と待とうという姿勢と捉えられる。

もちろんこの説を支持しても、生殖期間が終焉を迎え維持機能が衰退してくるとフリーラジカルによる細胞の損傷などが起こりやすくなると考えられる。 問題は何によって老化がもたらされるかではなく、どうして老化するのかという点であると思う。
この問題が解決したら、根本的に老化を防ぐことが可能になるかも知れない。

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