Your weight needs to be hitting the saddle on the "sitzbones", nowhere else. If the nose is even a few degrees too high, it will put pressure where you don't want it. Or, your saddle may not be wide enough or strong enough to support your weight.
Or, your saddle may be worn out. I just replaced my Terry Fly saddle after experiencing numbness on a couple of rides this summer. It had been comfortable for almost 3 years of riding (11,500 miles). But after the numbness, I checked to find the foam had gotten soft, and the pan had softened as well, making the saddle easy to press down in the center. It's my first cutout saddle; figure maybe these aren't as strong. At any rate, by pressing down and flexing the saddle by hand, it was obvious that it was turning into a hammock under my 190 lb load.
So, had the new Fly saddle on for the first long ride yesterday, and after 4 hours, all was well.....no numbness at all. My experience has been that all saddles seem to break down around 10K miles, but the wear is gradual and hard to detect until the dreaded numbness hits.