Progeria 是一种罕见的疾病，导致人们过早衰老。近年来，针对 Hutchinson-Gilford 综合征（一种主要的 Progeria 类型）的药物 lornafarnib 获得 FDA 批准。临床试验表明，该药物可显著降低患儿死亡率，但目前尚不清楚它能否延缓正常衰老。

👧 Progeria 是一种罕见疾病，导致患者过早衰老，例如儿童时期脱发、上学时出现皱纹，并可能在青少年时期因衰老而死亡。

🧪 近年来，针对 Hutchinson-Gilford 综合征（一种主要的 Progeria 类型）的药物 lornafarnib 获得 FDA 批准。临床试验表明，该药物可显著降低患儿死亡率，但目前尚不清楚它能否延缓正常衰老。

🧬 Progeria 是一种核纤层病，其特征是核纤层（细胞核的支撑结构）出现缺陷。核纤层由一种名为 lamin A 的蛋白质组成，而 Progeria 患者的基因突变导致他们产生一种称为 progerin 的缺陷蛋白。

🔬 由于细胞试图用缺陷的 progerin 构建核纤层，导致细胞核结构异常，无法保持正常形态。这可能解释了 Progeria 患者的加速衰老。

🤔 虽然 lornafarnib 在治疗 Progeria 方面取得了进展，但其对正常衰老的影响尚不清楚。进一步研究将有助于确定该药物是否可以延缓人类衰老过程。

https://astralcodexten.substack.com/p/what-do-treatments-for-accelerated

 

Progeria is a rare disease that makes people age unnaturally quickly. Babies born with progeria can lose their hair in toddlerhood, get wrinkles by grade school age, and die - apparently of old age - in their early teens. You can see a picture of a progeroid child here, though I don't recommend it.

There's been a lot of research on one important form - Hutchinson-Gilford Syndrome - and just last year, the FDA approved the first treatment, a drug called lornafarnib. In the study, a few hundred children averaging around 7 years old took the drug for two years; 3% died during that time. In an ad hoc group of untreated comparison children, about 30% died during the same period. I'm a little confused by the methodology - it seems like the "comparison children" were chosen partly because they died too early to get into the trial, which sounds like a pretty major confounder - but everyone seems to treat this as reasonable so I will assume they adjusted for this in some way. If that's true, then lornafarnib cuts mortality by 90%.

That's great for the 300 or so children worldwide with Hutchinson-Gilford progeria (it's a really rare disease). But none of the discussion about this answered the question I wanted to know: can lornafarnib also prevent normal aging?

After looking into this more, I find some evidence the the answer is no, but also some reasons why maybe it's less clear cut than that?

Hutchinson-Gilford progeria (I'll just say "progeria" from here on, even though that's kind of inaccurate) is what's called a laminopathy. It's a disease of the nuclear lamina, a weblike structure that helps support and give shape to the cell nucleus. The lamina is partly made of a protein called lamin A. Children with progeria have a mutation in the relevant gene; instead of producing lamin A, they produce a defective mutant protein called progerin. The cell tries to build the nuclear lamina out of defective progerin instead of normal lamin A, and as a result the cell nucleus is screwed up and can't maintain a normal shape.