4.3. The Measurement of Frailty Index

Frailty was measured using the validated 31-parameter mouse clinical frailty index as described previously [34,35]. Briefly, the clinical assessment includes evaluation of the integument, the musculoskeletal system, the vestibulocochlear/auditory systems, ocular and nasal systems, digestive system, urogenital system, respiratory system, signs of discomfort, body mass, and body surface temperature. The frailty index items including: (1) Alopecia (0.5: <25% fur loss, 1: >25% fur loss); (2) Fur color loss (0.5: <25% color change, 1: >25% color change); (3) Dermatitis (0.5: small section, 1: large multiple lesions); (4) Coat condition (0.5: not smooth/sleek, 1: very matted, ungroomed); (5) Loss of whiskers (0.5: some or color change, 1: no whiskers); (6) Kyphosis (0.5: some curvature, 1: strong curvature always); (7) Distended abdomen (0.5: slight bulge “W” shape, 1: clear bulge); (8) Vestibular disturbance (0.5: spinning when lowered, 1: head tilt at all times); (9) Cataracts/corneal opacity (0.5: small sections, 1: large areas of clouding); (10) Cataracts/corneal opacity (0.5: small sections, 1: large areas of clouding); (11) Eye discharge/swelling (0.5: minor discharge or swelling, 1: severe swelling or both eyes); (12) Microphthalmia (0.5: some shrinkage, 1: severe shrinkage or both eyes); (13) Malocclusions (0.5: excess or irregular teeth growth, 1: severe irregular growth); (14) Rectal prolapse (0.5: minor tissue protrusion, 1: severe tissue protrusion); (15) Penile prolapse (0.5: minor tissue protrusion, 1: severe tissue protrusion); (16) Mouse grimace scale (0.5: 1–2/5 items (whiskers, ears, cheeks, nose, eyes), 1: 3–5 items, doi:10.1038/nmeth.1455); (17) Piloerection (0.5: fur standing at neck, 1: fur standing on full body); (18) Tail stiffening (0: curling response, 0.5: some curling, 1: no response); (19) Gait (0: normal gait, 0.5: some abnormalities, especially on angle, 1: very abnormal gait); (20) Grip strength (0: as strong as a young mouse, 0.5: some reduction in grip, 1: no resistance against pull); (21) Body condition (0: normal, 0.5: too much or too little fat on hips, 1: hip bones very protruding or not felt at all); (22) Hearing loss (0: responds 3/3, 0.5: responds 1–2/3, 1: responds 0/3); (23) Vision loss (0: reaches from > 8 cm, 0.5: reaches from 2–8 cm, 1: reaches lower than 2 cm); (24) Menace reflex (0: responds 3/3, 0.5: responds 1–2/3, 1: responds 0/3); (25) Tremor (0: none, 0.5: some, especially on incline, 1: tremor at all times); (26) Growths (0: none, 0.5: <1 cm, 1: >1 cm or many); (27) Nasal discharge (0: none, 0.5: minor, 1: severe); (28) Diarrhea (0: none, 0.5: minor, 1: severe); (29) Breathing rate/depth (0: normal, 0.5: some slowing or irregularity, 1: very irregular, pauses); (30) Temperature score; (31) Body weight score. FI score is continuous from 0–1, with higher values indicating worse frailty [35]. For more detail see: http://frailtyclocks.sinclairlab.org/.