Given the physical condition of the individual:
A friend (female) would like a .22 semi-automatic pistol for defense and "Plinking".
She has weak wrists (senior citizen) and a Ruger Mk III with a 5.5 bull barrel is too heavy.
Sounds like a .22lr semi-auto pistol is a perfect fit for this individual with her particular physical challenges.
How about one of the 22 Tip-ups like the Taurus POLY PT-22 or the Beretta 21a ?
...These pistols are great for someone who doesnt have a lot of hand strength, because they load the first round by tipping up the barrel. No need to rack the slide.
^^^ +1
A former co-worker who happens to be a senior citizen with a touch of arthritis in her hands had the same dilemma presented by the OP. I took her to the range. I had her try to shoot and operate a Glock 19. While she could shoot it, the recoil impulse caused her some pain. Even with the proper push/pull slide racking technique, she didn't have the grip strength to rack the slide. Put a .38 Special revolver in her hands. The DA trigger pull + arthritis wasn't a good combo. Out went .22lr revolvers.
The one gun she had no problems with was the Taurus PT-22 with the tip up barrel. While .22lr wouldn't be anyone's first choice for self defense, sometimes physical limitations means it's the only choice. I think everyone will agree that having a firearm and training is better than having no firearm at all.