Built Differently, Down in the Membranes

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You might recall that different fatty acid or lipid composition in cell membranes was floated as a reason for the ninefold longevity of naked mole-rats over related rodent species. Plenty of oxidative stress in the older mole-rats, but little sign of biochemical damage resulting from it - in comparison to those other rodents long since aged to death, that is. Better, more damage-resistant building blocks down at the molecular level might be the cause:

Underlying causes of species differences in maximum life span (MLS) are unknown, although differential vulnerability of membrane phospholipids to peroxidation is implicated. ... membranes of longer-living, larger mammals have less polyunsaturated fatty acid (PUFA). ... Both species had similar amounts of membrane total unsaturated fatty acids; however, mice had 9 times more docosahexaenoic acid (DHA). Because this n-3PUFA is most susceptible to lipid peroxidation, mole-rat membranes are substantially more resistant to oxidative stress than are mice membranes ... suggesting that membrane phospholipid composition is an important determinant of longevity.

A forthcoming Rejuvenation Research paper discusses the results of a similar consideration of cell membrane differences and longevity within the human species:

Fatty Acid Profile of Erythrocyte Membranes As Possible Biomarker of Longevity:

Offspring of long-lived individuals are a useful model to discover biomarkers of longevity. The lipid composition of erythrocyte membranes from 41 nonagenarian offspring was compared with 30 matched controls. Genetic loci were also tested in 280 centenarians and 280 controls to verify a potential genetic predisposition in determining unique lipid profile.
...

Erythrocyte membranes from nonagenarian offspring had significantly higher content of C16:1 n-7, trans C18:1 n-9, and total trans-fatty acids, and reduced content of C18:2 n-6 and C20:4 n-6.

...

We concluded that erythrocyte membranes derived from nonagenarian offspring have a different lipid composition (reduced lipid peroxidation and increased membrane integrity) to that of the general population.

Note there again - reduced lipid peroxidation, as for the naked mole-rats, and therefore more resistant to oxidative stress. This is quite an interesting line of research, demonstrating some plausible indications of a structural contribution to longevity at the cellular level. I'm sure we'll be seeing more of this in the future, as research and debate continues.