Many Methods of Modestly Slowing Aging in Laboratory Species are Gender Specific

Over the past twenty years researchers have demonstrated a great many ways to slightly slow aging in short-lived laboratory species: flies, worms, and mice. As a general rule these are largely irrelevant to the future of human longevity, however. They are adjustments to the operation of metabolism, something that is expensive and challenging to understand well enough to do safely in humans, and the beneficial effects are small (and in many cases unreliable and disputed) even when operating over the entire life span. Trying to make human therapies of these results is a dead end in comparison to the approach of repairing age-related cell and tissue damage. Many of the methods of slightly slowing aging through metabolic alterations produce different results in males and females, which is probably to be expected given that there are differences in metabolism between the genders that are at least as large as the changes produced by some of these interventions.

Analyzing years of previous research on dietary and pharmaceutical tests on flies and mice, researchers showed that aging interventions can have opposite effects on mortality rates in males versus females. The findings appear consistent with data gathered on humans as well. Researchers found that treating flies with the steroid hormone mifespristone/RU486 (used in humans for terminating pregnancy) decreased egg production in females while increasing longevity. Similar effects were seen by tweaking the diets of flies and mice, but the effects were sometimes opposite in males versus females.

Increasing life span also increased the acceleration of age-dependent mortality rate of the population. That's evidence of a strong Strehler-Mildvan relationship, which is described by the Gompertz equation, a model for mortality named for the British mathematician who first suggested it in 1825. Here's what that means: Suppose you could create a graph of the mortality rate of everyone born in a single year - from birth until the last person died. You'd see two key things: Off the bat, there'd be a small number of individuals dying here and there - typically due to infections and pathogens. That's non-age-driven mortality. Then, as the group aged, you'd see the mortality rate rise exponentially until the last person died. This acceleration is thought to represent true aging - the inexplicable breakdown of the body over time. "We all speculate, but no one has really figured out what the cause of that acceleration is. Our results show that dietary and genetic interventions sometimes have opposite effects on that acceleration in males versus females."

What the Strehler-Mildvan relationship implies is that this equation is affected by the mixture of strong and frail individuals in a population - and that if you tweak the mixture, the mortality rates will adjust accordingly. "There are weaker, low-vitality individuals in the population and if you kill them off, you're left with high-vitality individuals and the population has a slow mortality acceleration with age. The relationship was so striking in how robust it was in the data we analyzed. I've never seen numbers like that. It confirms that this is a very fundamental relationship."

The findings would also seem to support the antagonistic pleiotropy model for aging, proposed in 1957. Pleiotropy refers to a single gene that affects multiple physical characteristics. In part, the model tries to explain why our bodies ultimately break down and die. Natural selection might select for a gene that creates a fatal flaw later in life if it offers some significant benefit earlier -- that is, if it helps individuals reproduce successfully, it's beneficial to the species even if it does ultimately shorten the individual's life span. The mifespristone intervention appears to prevent such a trade-off between life span and reproductive ability - albeit, a sex-dependent one.

Link: http://news.usc.edu/92062/some-aging-treatments-shown-to-have-opposite-effects-on-males-and-females/