The Little-Known Curses of the Y Chromosome

The male sex is determined by the presence of the Y chromosome, which contains a region of DNA that encodes a gene known as the sex-determining region of Y that promotes the formation of male gonads. From then on, males (of all species) face a challenging life that always ends earlier than that of females. Consistent with this notion, individuals with two Y chromosomes (XYY) have a lifespan that is reduced by approximately ten years.

In contrast, having an extra X chromosome (XXY) only reduces the expected lifespan by about two years. Let’s look at two important examples of how the Y chromosome can either accelerate aging or promote longevity: the characteristics of the male immune response and the tendency of male bodies to waste too much energy as heat.

The Male Immune Response

A high density of immune-related genes is located on the X chromosome. Therefore, given the crucial role of the immune system in achieving longevity, it is not surprising that women live longer than men. In contrast, men, having only one X chromosome, have an inappropriately higher inflammatory response, increased cardiovascular disease risk, and a much greater risk of inflammation-induced atherosclerotic plaque formation, all due to the response of their limited inflammation-related genes.

The presence of the Y chromosome also increases the risk of the autoimmune-based origin of multiple sclerosis. In addition, men develop AIDS faster and, unfortunately, show resistance to antiretroviral therapy not seen in women. Even older women fare better than men; older females exhibit greater resilience to infections than older males.

Being Too Hot

Thanks to the Y chromosome, males have lots of testosterone circulating in their bodies. In addition to its many well-known behavioral functions, testosterone significantly alters how males metabolize food. Males produce too much in their cells during normal respiration. Due to its effects on a specialized protein called Uncoupling Protein or Thermogenin, testosterone makes the normal food-to-energy conversion process in mitochondria inefficient—cells waste more energy as heat, making men feel warm almost all the time. Males, to the chagrin of females, can lose weight by simply sitting still and watching football. In contrast, women who lack the mitochondrial uncoupling actions of testosterone are forced to lose weight the old-fashioned way by not consuming as many calories.

Unfortunately, for males, wasting calories to produce heat has some negative long-term consequences. First, males need to consume more calories per day than females and generate more harmful reactive oxygen-free radicals, ROS. These ROS are harmful to the body, negatively affect men’s health, and reduce their longevity, as compared to women.

Males of all studied species, including spiders, birds, bees, dogs, and cats, generally do not live as long as females due to all of these ROS floating around. This is true even for species with a very short life span, such as a fly. Male flies of one species have an average maximum life span of five days; the females of the same species have an average maximum life span of seven days. In contrast to males, females waste less energy as heat, consume fewer calories daily to survive, and produce fewer ROS, all of which benefit female brain health and longevity. Females also feel colder.

You can easily see the paradox here. Males must eat to survive; however, accessing the energy stored in food produces ROS. Thanks to testosterone and all of those mitochondria in every cell of their body, males, all things being equal, always die sooner than females. (See my book Your Brain on Exercise for a discussion on how exercise complicates the aging process.)

The social and cultural roles and expectations associated with being male have been extensively studied and clearly shape the aging process. However, based solely on the influence of the Y chromosome, males have a disadvantage compared to females in achieving a longer lifespan.