What Isolation did to Madara

Madara Aged Dramatically. He left the village 66 years ago. Nagato was born 35 years ago. 66-35=31. Let’s assume Madara gave Nagato his eyes while Nagato was under 10 years old. In 31 to 41 years Madara reached an age where he was close to the end of his natural life span.

His dramatic aging doesn’t seem so strange when you take the following points into consideration:

• Madara lived in social/physical isolation for 31 years possibly going out only for food, could be he dealt with small villages
  
• There is very little in his cave - his weapons, cloaks; little stimulation and it’s a place deprived of sunlight and later fresh air when he blocks all entrances with a boulder.
• His goal of awakening the Rinnegan would look like a failed attempt since he had no idea when it would awaken and by the time it did he had physically wasted away; plagued by feelings of depression, failure for decades
• Minimal training with chakra, lowered physical training and conditioning

Loneliness creates many measurable differences:

• Diminished physical activity, motor function
• Symptoms of depression
• Disrupted sleep and daytime dysfunction
• Impaired mental and cognitive function
• Altered gene expression related to anti-inflammatory responses, altered immunity

“When you feel pain… you know that you are alive.” is a product of the years he lived in isolation.

Here is an interesting article on the subject of extreme isolation: How Extreme Isolation Warps the Mind. This is more relevant to Madara’s later years when he is old and possessing little mobility. Here is an excerpt from the article: 

[…] isolating six volunteers for 48 hours in sound-proofed rooms in a former nuclear bunker. The results were similar. The volunteers suffered anxiety, extreme emotions, paranoia and significant deterioration in their mental functioning. They also hallucinated […]

Depression ages you faster, Effects of Light Deprivation

Notice the lines on Madara’s face. Compare it to the lines on the faces of Hiruzen, Danzo, Homura and Koharu. They are around 69 years old. Also note Tsunade’s face when her appearance-altering technique had faded during the war. Her biological age was far beyond her 54/55 years of age. She looks far older than even Uzumaki Mito had in her old age.