Dwelling in Probabilities

• Newman, Emma. Planetfall. Renata Ghali follows her beloved friend to their new planetary home in search of their vision of God, only to have things go very wrong.

• Older, Daniel José. "The Passing" in Salsa Nocturna and Other Stories. Elderly Latina story keeper fights to keep stories alive and remembered.
• Page, Shannon Page and Lake, Jay. Our Lady of the Islands. Fantasy with two powerful middle-aged female protagonists, Sian and Arian, who must work together to save their land and their loved ones.
• Piercy, Marge. Malkah Shipman in He, She and It is a computer programmer in a postapocalyptic future who must work with her daughter and her beloved android to fight cyberpirates and preserve their community.
• Pollack, Gillian. Ms. Cellophane. Older female protagonist on fantastical journey of self-discovery.
• Pratchett, Terry. Granny Weatherwax and Nanny Ogg in The Wyrd Sisters, and other Witches novels, are the two older witches (The Crone and The Mother) of Pratchett's wild popular trio of Discworld witches.
• Rambo, Cat. "Grandmother: Farther Than Tomorrow." Short story about a century-old pirate called out of retirement to save her planet.
• Randall, Marta. The Sword of Winter. Lyeth is a courier for a dying tyrant she despises, trying to negotiate a chaotic kingsdom and a complex series of plots (I'm reading her age into this; she feels "middle-aged" to me).
• Rickert, Mary. The Memory Garden. Nan, her friends and her granddaughter come to terms with their pasts, their futures and the ghosts of both.
• Richardson, E.E. Under the Skin and Disturbed Earth. Claire Pierce, head of the North Yorkshire Police Ritual Crime Unit, takes on the apocalypse and paranormal perils.
• Rigney, Mark. "Mayor of a Flourishing City" (Betwixt Magazine, Issue 1, 2014). Mayor Janet Bentham will do anything for her city...or will she?
• Robins, Madeleine. Barbara McGrath in The Stone War is in her early 60s when she has to help rebuild NYC after an apocalyptic collapse (Multiple POV). Zenia Mavroandrades in "The Boarder" (Asimov's, 1984) has to contend with a new and alien roommate.Vivey in "La Vie en Ronde" (Starlight 3) experiences a strange illness that opens a doorway to a new world.
• Robinson, Kim Stanley. Mars Trilogy, ensemble cast with older characters.
• Robson, Kelly. "Gods, Monsters and the Lucky Peach." A female scientist doing habitat restoration in an apocalyptic future gets the opportunity to travel back in time.
• Ruff, Matt. Lovecraft Country. Multiple POV. One of the writers for The Safe Negro Travel Guide, Letitia, is in her 40s for much of the book.
• Russ, Joanna. Abbess Radegunde in "Souls" (Extraordinary People). Older female protagonist who confronts a Viking attack on a medieval convent. Janet Evason in “When It Changed.” Middle-aged protagonist on all-female planet wrestling with the impact of the arrival of male astronauts from Earth.
• Rustad, Merc. "Batteries for Your Doombot 5000 are Not Included." So You Want to be a Robot: 21 Stories by Merc Rustad. An aging supervillain joins forces with her nemesis to find her lost love.
• Salaam, Kiini Ibura."Two Become One" in To Shape the Dark. Multiple POV story. Meherenmet and Amagasat struggle for control of the former's destiny, using Meherenmet's apprentice, K, and a creature of her own creation as pawns.
  
• Sargent, Pamela. “Heart Flowers.” Post-apocalyptic SF with old female protagonist.
• Sanderson, Brandon. Shadows for Silence in the Forests of Hell. Middle-aged  innkeeper Silence Montane has a secret identity as a bounty hunter.
• Sato, Yuya. Dendera. 70 year old Kayu Saitoh leaves her village to go and wait to die on the nearby mountain, in accordance with custom. But things don't quite turn out that way when she stumbles onto a not-quite-utopian society built by elderly women that is under attack on multiple levels.
• Saxton, Josephine. "Big Operation on Altair Three" in Despatches from the Frontiers of the Female Mind, edited by Jen Green and Sarah Lefanu (1985). Aging ad exec in a near future dystopia contemplates a career change. See also Magdalen in Queen of the States.
  
• Scalzi, John. Old Man's War . Military SF series in which characters sign up for the Colonial Defense Forces in their sixties, never to return to Earth.
• Shawl, Nisi. Everfair. Multiple POV alternate history/steampunk set in the what would be, in our timeline, the Belgian Congo. 2 of the protagonists are women over 40.
• Shoulders, Felicity. "Conditional Love" in Asimov's, January, 2010. Dr. Grace Stellar works in a lab facility that "fixes" genetically modified children.
• Springer, Nancy. Fair Peril, Larque on the Wing and Plumage. Middle-aged female protagonists exploring gender, aging and magic.
• Starhawk. Fifth Sacred Thing. Post-apocalyptic novel with multiple viewpoint characters, including 98 year old Maya Greenwood.
• Stirling, S.M. Captain Marian Alston-Kurlelo in Island of the Sea of Time, etc. Alternate history with an ensemble cast. Marian is the middle-aged African-American lesbian captain of a Coast Guard vessel brought to an alternate Nantucket.
• Tarr, Judith. Khalida in Forgotten Suns is a 40+ year old former military intelligence officer hiding out from her past when she is forced back into service.
• Valente, Catherynne M. Yume no Hon: The Book of Dreams. Elderly Japanese female hermit as the POV character.
• Vernon, Ursula. “Jackalope Wives” and “Pocosin” in Apex Magazine. Different older women protagonists in both; Grandma Harken in “Jackalope Wives” turns shapeshifter myths on their heads.
• Walton, Jo. My Real Children. Alternate history featuring two different versions of character Pat Cowan’s life, starting at its end when she is an elderly woman.
• Warner, Sylvia Townsend. Lolly Willowes. Middle-aged English spinster sells her soul to the devil in order to become a witch. Fantasy/satire
• Warrington, Freda. Midsummer Night. Multiple POV fantasy. Dame Juliana is an artist in her sixties struggling to gain mastery over her art and her powers.
• Walters, Damien Angelica. "When the Lady Speaks." Fortune-teller Marian hopes to use her powers to save her injured daughter.
• Wells, Martha. Wheel of the Infinite. Maskelle is recalled from a long exile to save her world and the god she serves.
• Wilder, Cherry. “Mab Gallen Recalled.” Retired ship’s medical officer reminiscing about her life and previous events.
• Wilkins, Connie. “Windskimmer” in Hellebore and Rue: Tales of Queer Women and Magic. Two female magic users reunite to stop a magic-fueled environmental plague.
• Williams, Jen. The Ninth Rain. Explorer Lady Vincenze "Vintage" de Grazon and her companions are drawn into a magical conspiracy to revive an ancient empire. Multiple POV.
• Williams, Liz. The Ghost Sister. Female anthropologist comes into contact with a cultural outcast on a distant planet.
• Windling, Terri. The Wood Wife. Middle-aged woman discovers art and magic in the SW.
• Winter Well: Speculative Novellas About Older Women edited by Kay Holt.
• Wonder City Stories - Multiple POV, serial story featuring multiple older women characters including Renata Scott and Suzanne Feldstein. Interludes #1, 2, and 7 feature middle-aged or elderly women as leads (Lady Justice, the Fat Lady, and Pearl Wong, respectively).
• Wrede, Patricia. Granny Carry/Tenerial Ka'Riatha. Elderly woman who is the magical guardian of the traditions and magic of the early inhabitants of the city of Liavek. Stories collected in Points of Departure.
• Wright, Helen S. A Matter of Oaths. Commander Rallya is in her 60s or 70s,  commands her own spaceship and has just taken on a new crew member with some serious baggage. Lesbian/bi/pan characters.
• Wymore,Teresa. Darklaw. Erotic epic fantasy with two lesbian protagonists, one of whom is in her forties.
• Yarbro, Chelsea Quinn. “The Generalissimo’s Butterfly” in Cautionary Tales. Older female engineer has fallen from grace with the dictator she helped keep in power.

Also see this interesting list/discussions on Tor. Com: Where are the Older Women? And Older Women as Lead Characters in Urban Fantasy.
 as well as the following excellent and related essays Where are the Wise Crones in Science Fiction? by Athena Andreadis, "Hands" by Kari Sperring and "No More Dried Up Spinsters" by Nancy Jane Moore. Harry Connolly also touches upon the difficulty of getting publishers to pick up novels with older female protagonists in his essay Helpless in the Face of Your Enemy. Helen S. Wright wrote an article for The Portalist on the theme of "What Happens When an Old Woman Steals Your Story?"

And honorable mentions, since they are not protagonists, but are fairly unique in postapocalyptic sf, the matriarchal bikers in Mad Max: Fury Road.