Эрдэмтэд эсийн биологийн насыг ухраах боломжтой “дахин програмчлах” аргыг туршилтаар баталлаа.
Хөгшрөлтийг молекулын түвшинд эсийн геном дахь химийн тэмдэглэгээ алдагдах үйл явц гэж үздэг. 2006 онд нээгдсэн Яманакагийн хүчин зүйлс (Oct3/4, Sox2, Klf4, c-Myc) хэмээх дөрвөн уургийг ашиглан эсийг бүрэн өөрчилж, үр хөврөлийн төлөвт шилжүүлэх боломжтой болсон. Харин судлаачид сүүлийн үед энэхүү үйл явцыг хэсэгчлэн, хяналттайгаар хэрэгжүүлснээр эсийн анхдагч шинж чанарыг алдагдуулахгүйгээр биологийн насыг нь залуужуулах арга замыг судалж байна.
Харвардын Анагаах ухааны сургуулийн судлаачдын 2024 онд Nature Communications сэтгүүлд нийтэлсэн тойм судалгаагаар хулгана дээр хийсэн туршилтуудын үр дүнг танилцуулжээ. Эдгээр туршилтаар Яманакагийн хүчин зүйлсийг богино хугацаанд, үе шаттайгаар идэвхжүүлэхэд хөгшрөлтийн эсрэг эерэг өөрчлөлтүүд ажиглагдсан байна. Тухайлбал, хөгшрөлт хурдасгасан загварын хулгануудын дундаж наслалтыг 33 хувиар уртасгаж, харин өндөр настай хулганууд дээр c-Myc уургийг оруулалгүйгээр хийсэн генетик эмчилгээ нь наслалтыг 109 хувиар нэмэгдүүлжээ.
Генетик аргын эрсдэлийг тооцон судлаачид химийн бодис ашиглан эсийг залуужуулах хувилбарыг мөн судалж байна. Химийн найрлагатай бэлдмэл ашиглан C. elegans хорхойн наслалтыг 42.1 хувиар уртасгасан бөгөөд хулганы фибробласт эсүүд дээр хийсэн туршилтаар эсийн үйл ажиллагаа сайжирч, биологийн нас залуужсан үзүүлэлтүүд бүртгэгджээ. Гэсэн хэдий ч энэ төрлийн эмчилгээ нь хавдрын эрсдэл үүсгэж болзошгүй, мөн лабораторийн нөхцөлөөс амьд бие махбодод шилжүүлэх үр ашиг хангалтгүй зэрэг шийдвэрлэх шаардлагатай олон асуудал үлдээд байна.
Дэлгэрэнгүйг эх сурвалжаас харах
↓Эх сурвалжийг нээх ↓
Aging, at its most fundamental level, is a molecular process. Chemical marks on the genome shift and lose fidelity over time, disrupting how cells function. A growing body of research now suggests those marks can be partially reset, pushing a cell’s biological age measurably backward.
The approach, known as reprogramming-induced rejuvenation (RIR), builds on a 2006 discovery showing that four specific proteins introduced into adult cells could erase their identities entirely, returning them to an embryonic-like state.
The four proteins, called the Yamanaka factors, are Oct3/4, Sox2, Klf4, and c-Myc. Full reprogramming with these factors wipes out a cell’s identity completely. What researchers have more recently explored is whether a partial, carefully timed version of that process can roll back biological age without destroying what the cell is.
The Epigenome Records and Accumulates Age
To understand why this matters, it helps to know what the epigenome does. The epigenome is the collection of chemical compounds sitting on or near DNA in each cell, telling genes when to activate, when to stay silent, and where to do either. As the National Human Genome Research Institute explains, these marks differ between cell types and can be passed from cell to cell as cells divide.
With age, this marking system degrades. Patterns that once held steady become noisy or confused, disrupting cellular homeostasis. Scientists have developed epigenetic clocks, tools that read DNA methylation patterns and estimate a cell’s biological age, which can diverge significantly from its chronological age.
A key observation driving rejuvenation research is that natural epigenetic resets occur during early embryogenesis and during full cell reprogramming. If that signal can be applied partially, a cell might be made younger without being made formless.
Partial Reprogramming Reverses Aging Marks in Mice
Much of the in vivo evidence comes from mouse experiments reviewed in a 2024 perspective published in Nature Communications by researchers at Harvard Medical School. Those studies used animals engineered to carry inducible Yamanaka factors controlled by a drug switch. Administering the drug in short cycles, rather than continuously, allowed the factors to activate briefly before switching off, preventing full erasure of cellular identity.
In progeric mice, a model of accelerated aging, cyclic administration extended median lifespan by 33% compared to untreated controls, reducing mitochondrial reactive oxygen species and restoring chromatin marks associated with younger cells. A separate study applying cyclic reprogramming to normal mice found that transcriptome, lipidome, and metabolome patterns across multiple tissues shifted toward younger states, and skin regeneration capacity increased.
A third study delivered OSK factors via gene therapy to very old mice, omitting c-Myc to reduce cancer risk, and extended remaining lifespan by 109% compared to untreated animals of the same age. Frailty scores in treated mice also improved.
Tissue-specific applications produced notable results as well. When OSK factors were delivered to retinal ganglion cells in aged mice and glaucoma models, visual function partially recovered. Unlike whole-body experiments, continuous factor expression in the eye did not produce teratomas even after ten to eighteen months of treatment.
Chemical Reprogramming Offers a Non-Genetic Path
Delivering genetic instructions safely across an entire living body remains technically difficult, and cancer risk from prolonged factor expression is a genuine concern. Continuous OSKM expression across all tissues has caused liver and intestinal failure in mice, and uncontrolled reprogramming has produced teratomas.
These limitations have pushed researchers toward chemical reprogramming, which uses small molecules rather than genetic factors. A two-chemical procedure extended lifespan in C. elegans by 42.1%, reduced DNA damage, and improved several epigenetic aging marks, according to studies cited in the Nature Communications review. Partial chemical reprogramming of mouse fibroblasts using a seven-compound cocktail also showed multi-omic signatures of rejuvenation, including improved mitochondrial function and reductions in aging-associated metabolites, with epigenetic clocks registering a measurable decrease in biological age.
One meaningful difference between chemical and factor-based approaches emerged around the p53 pathway. OSKM reprogramming suppresses p53, a major cell-cycle regulator and tumor suppressor, while the chemical cocktail upregulates it. The safety implications of that difference are still being worked through.
Safety Concerns and Open Questions
The Nature Communications perspective is candid about the obstacles. Even a single fully reprogrammed cell in a living organism carries a teratoma risk. Reprogramming can lift suppressive epigenetic marks that normally keep cancer-associated genes quiet, and studies show that iPSC reprogramming enriches for cell clones carrying mutations in genes tied to cell death, cell cycle control, and pluripotency. Partial reprogramming may not raise instability at the single-cell level, but could shift a population toward higher risk overall.
Efficiency also remains low. In cell culture, only about 25% of cells successfully undergo partial reprogramming under current protocols. The gap between what works in a dish and what works in a living body remains one of the field’s central problems.
There are also open questions about what epigenetic clocks actually measure. Several widely used clocks correlate with chronological age but may capture adaptive as well as damaging changes. A newer class of clocks designed to track only CpG sites with a causal relationship to aging could eventually allow more precise evaluation of whether a treatment genuinely reverses cellular damage, or simply shifts markers without improving function.
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