Three unusual reasons that help animals live incredibly longer lives

Calorie restriction data on primates

Moreover, prolonged calorie restriction has been shown to reduce age-associated disease in rodents and monkeys (12, 13). For example, researchers followed Rhesus monkeys for 20 years. Fifty percent of the control fed animals survived compared with 80% survival of the animals that were given 30% less calories per day. In addition, the calorie-restricted animals had less evidence of  diabetes, cancer, cardiovascular disease, and brain atrophy (13).

In humans, studies on calorie restriction over 2 years show improvements in multiple metabolic  markers (14). There is even evidence that atherosclerosis (hardening of the arteries) can be reversed through calorie restriction (15). In that study, eighteen people who had been on a calorie restricted diet for an average of 6 years. were compared to a control group. Their carotid artery wall thickness was 40% lower than the control group (15). Preventing or minimizing aging as well as increasing longevity through dietary or therapeutic means is the holy grail to combat aging-related disease such as dementia, cardiac disease, and cancer (16, 17, 18).

Cool creatures

Multiple species of animals have adapted to cold weather. The ones that come to mind are reptiles, since they are cold-blooded creatures (19).  Data on reptiles in the wild has found that colder temperatures encourage longer lives (19,20). Keep in mind that not only reptiles enjoy longevity benefits of colder temperatures: crustaceans, snails, fish, and amphibians (frogs, toads, salamanders) also demonstrate longer lives with colder temperatures (20, 21, 22, 23, 24).

One cool example that highlights the effect of cold temperatures on longevity is that of the freshwater pearl mussel. This species of bivalve mollusk is found at different latitudes. The animals that live in the arctic Russian rivers exhibit five times longer lifespans compared to the same species that live in the warmer river waters in Spain (25). The effect of latitude on longevity has been documented for other cold-blooded species (21).

Some experimental data

What about experiments that demonstrate longevity as a result of colder temperatures? Here are two:

1. flies raised at  18 °C lived 148 days versus flies raised at 12 °C lived 247 days, 66% longer lifespan (26).
2. Transgenic mice were programmed to have elevated hypothalamic temperature. This elevation in the central thermostat resulted in a 0.3° to 0.5°C reduction of the core body temperature. Even with this modest decrease in body temperature, the experimental mice had a greater median life span (12% increase in males; 20% increase in females) (27).  

Finally, animals that use torpor (like reptiles) or hibernation (like bats) to reduce their metabolic rate and survive harsh winters show the same physiologic and biochemical changes as rodents that undergo calorie restriction. Torpor and hibernation reduces the animal's need for food, decreases its predator risk, and depresses its body temperature (28, 29). Needless to say, animals that exhibit significant reductions in core body temperatures during hibernation enjoy longer lives (29).

Other creatures with longer lives

Other creatures well known for their longevity have adapted to intermittent hypoxia when under water or in subterranean environments. These include Greenland sharks, Bowhead whales , Tuataras (a dinosaur-like lizard unique to New Zealand),  quahog clams, turtles, diving seals, arctic ground squirrels, sponges, certain fish (crucian carp), and naked mole rats(1, 4, 31, 32, 33). 

Moreover, experiments using hypoxic conditions clearly show that animals will have longer lives (4): 

• Mice exposed to chronic hypoxia for ~ 1 month showed gene expression patterns of animals that underwent calorie restriction
• A microscopic aquatic animal, the rotifer (Brachionus manjavacas) showed doubling of its lifespan when exposed to hypoxic conditions
• Flies (Drosophila) lived longer lives under moderate hypoxic conditions 

Hypoxic environment effect on humans

Finally, studies have examined human populations that live in chronic hypoxic conditions. For example, people living in the Tibetan Plateau tend to have longer lives than older people living at lower altitudes. In support of this, studies have also documented that Tibetans showed up-regulation of longevity-associated genes. This is the same pattern that has been found in model animals under hypoxic conditions (34). Interestingly, Tibetans also had evidence for a shift towards anaerobic metabolism of glucose (35).

What doesn't kill you makes you live longer

As animals adapt, the adaptation selects genes that are linked to longevity and/or the adaptation-related genes themselves encourage the development of longer lives.

I have to say, though, that experiments that  change the environment can induce "healthier" and longer living cells even in short term experiments (38). This suggests that an adaptation process may not need to be invoked. Thus, decreasing calorie intake, placing animals in cold or low oxygen environments shows relatively quick effects at the cellular level, presumably prior to an adaptation response.  This suggests that those cold, food-scarce, and oxygen-poor environments may be good for cells and organisms. 

As has been shown throughout this article, there is a plethora of data supporting this. Longevity genes and proteins are up-regulated when animals are in cold, resource-poor, and hypoxic environments (1).

Cellular hyper-function and Clean cupboards

Two theories of aging makes sense of this: 

1. Cellular Hyperfunction thesis: programs that support growth and development don't shut off when the organism is fully grown. Keeping the growth program in the on-switch position promotes cellular hyperfunction, hyperplasia, and hypertrophy (36, 37).
2. "Clean cupboards" thesis: This suggests that cells benefit from environments that allow the cells to get rid of excess stuff, including old cells, misfolded proteins, etc (39)

Basically, environmental factors select for animals that can adapt to the change in the environment. And once those animals have adapted, those environmental factors promote cellular longevity. What doesn't kill you not only makes you stronger, it makes you live longer.