In the orchestra of aging, every instrument has its own part. The protein SIRT6 was long considered the chief conductor of longevity: with plenty of it, cells live longer. But when researchers compared gene activity data from humans, mice, rats, macaques, pigs, and fruit flies, it turned out that SIRT6 plays different music in different organisms.
In people, SIRT6 levels in skin cells barely change until age 80, then drop sharply. But not for everyone: in some long-lived individuals it stays high, while in others it falls low, like a lottery. In Alzheimer's disease, SIRT6 drops in some brain cells and rises in others. So measuring SIRT6 as a universal marker of aging doesn't work: it only reveals local problems.
In skin fibroblasts from people over 80, SIRT6 expression lands in the top 2.4% of genes with the greatest increase in variability, meaning that in some long-lived individuals it is high and in others low, which feels a lot like a lottery.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.