Aging Biochemistry and the Comparison of Rodents

Researchers are beginning to develop a more detailed understanding as to why different species of a similar size and taxonomy can have widely varying rates of aging. You might recall that in the case of the renowned and long-lived naked mole rat, there are noteworthy differences in the biochemicals making up some of the cellular machine most vulnerable to oxidative damage. That oxidative damage is a part of the many types of damage to living machinery that cause aging - it can't hurt to suffer less of it, or so present science strongly suggests. Along those lines, here's a couple of more recent papers:

Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity:

Vascular aging is characterized by increased oxidative stress, impaired nitric oxide (NO) bioavailability and enhanced apoptotic cell death. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower production of reactive oxygen species (ROS) and/or superior resistance to oxidative stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), that show a more than twofold difference in maximum lifespan potential (MLSP = 8 and 3.5 years, respectively).


increased lifespan potential in P. leucopus is associated with a decreased cellular ROS generation and increased oxidative stress resistance, which accords with the prediction of the oxidative stress hypothesis of aging.

Life and death: metabolic rate, membrane composition, and life span of animals:

Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging.

However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species.

When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span.

If a somewhat more resistant cellular composition - building block molecules that are harder to damage with those dangerous free radicals churned out by your metabolism - can explain such wide variations in life span, think how much better we can do by repairing the damage at regular intervals. There is plenty of evidence to suggest that manipulating the rate of oxidative damage in precise ways in mammals can have meaningful effects on healthy life span, after all.

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