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The Mastiff should at all stages of development show the breed characteristics of massiveness and sound, if cumbersome, movement. The Mastiff is a particularly large dog demanding correct diet and exercise. Excessive running is not recommended for the first two years of the dog's life, in order not to damage the growth plates in the joints of this heavy and fast-growing dog, which in some weeks may gain over 5 lbs. However, regular exercise must be maintained throughout the dog's life to discourage slothful behaviour and to prevent a number of health problems. A soft surface is recommended for the dog to sleep on to prevent the development of calluses, arthritis, and hygroma (an acute inflammatory swelling). Due to the breed's large size, puppies may potentially be smothered or crushed by the mother during nursing. A whelping box, along with careful monitoring can prevent such accidents. The average lifespan of the Mastiff is about 7 years although it's not uncommon for some to live to 10–11 years.

Major problems can include hip dysplasia and gastric torsion. Minor problems include obesityosteosarcoma, and cystinuria. Problems only occasionally found include cardiomyopathy, allergies, vaginal hyperplasia, cruciate ligament rupture, hypothyroidism, OCD, entropion, progressive retinal atrophy (PRA), and persistent pupillary membranes (PPM).

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