Table 1 ∣.

Summary of studies testing rejuvenation interventions at midlife or later in naturally ageing mice

Intervention	Age at intervention (months)	Metric output	Comparison points (control)	Ref.
Blood factors
Parabiosis	2–3, 19–26	Skeletal muscle (MuSC) and liver regeneration	Old-old and young-young parabionts	17
Parabiosis	4–6, 24–26	Muscle regeneration (MuSC and fibrosis)	Old-old and young-young parabionts	16
Parabiosis	3–4, 18–20	Neurogenesis and cognitive function	Old-old and young-young parabionts	21
Parabiosis	1–2, 10–12	Spinal cord remyelination	Middle-aged-middle-aged and young-young parabionts	24
Parabiosis	2, 23	Cardiac metrics	Old-old and young-young parabionts	18
Parabiosis	2, 15–16 or 21	Neurogenesis and cognitive function	Old-old and young-young parabionts	22
Parabiosis	2–3, 22–24	Muscle regeneration (MuSC) and function	Old-old and young-young parabionts	20
Parabiosis	3, 18	Synaptic plasticity and gene expression	Old-old parabionts	25
Parabiosis	3, 19	Bone regeneration	Old-old and young-young parabionts	19
Parabiosis	3, 18	Neurogenesis and cognitive function	Young-young parabionts	23
Young blood injection	18	Cognitive function and gene expression	Old blood	25
Human plasma injection (cord, young and elderly)	8–10, 13–14	Neuronal and cognitive functions and gene expression	Age-matched vehicle control, young (22 years of age) and old (66 years of age) human plasma
TIMP2 administration	18	Synaptic plasticity and cognitive functions	Age-matched vehicle control	26
Oxytocin administration	2–4, 22–24	Muscle regeneration (MuSC and fibrosis)	Age-matched vehicle and antagonist (only young) control	36
GDF11 administration	23–24	Cardiac metrics	Age-matched vehicle control	18
GDF11 administration	21–23	Neurogenesis and cognitive function	Age-matched vehicle control	22
GDF11 administration	2–3, 22–24	Muscle regeneration (MuSC) and function	Age-matched vehicle control	20
GDF11 administration	23	Muscle regeneration (MuSC)	Age-matched vehicle control	34
GDF11 administration	24	Cardiac metrics and function	2 months of age, 3 months of age and age-matched vehicle treated	33
GDF11 administration	2, 22	Cardiac metrics and body weight	Age-matched vehicle control	32
Metabolic manipulation
Short-term dietary restriction	5–8, 28–30	Vasculature metrics	Age-matched ad libitum	43
Short-term dietary restriction	2, 18	Skeletal muscle (MuSC)	Age-matched ad libitum	7
Fasting-mimicking diet	16	Organ size and regeneration	16 months of age and age-matched ad libitum	5
Fasting-mimicking diet	16	Immunosenescence	4 months of age, 16 months of age and age-matched ad libitum	5
Fasting-mimicking diet	16	Cognitive function	Age-matched ad libitum	5
Fasting-mimicking diet	16	Bone density	12 months of age and age-matched ad libitum	5
Fasting-mimicking diet	16	Cancer and inflammation	Age-matched ad libitum	5
Ketogenic diet	12	Physiological and metabolic metrics; physical, behaviour and cognitive functions	Age-matched ad libitum and low-carbohydrate non-ketogenic
Ketogenic diet	12–14	Cognitive and motor function and frailty index	12 months of age and age-matched ad libitum	8
Ketogenic diet	12–14	Cognitive and motor function	12 months of age and age-matched ad libitum	8
Rapamycin	22	Immune system (HSC and immunity)	2 months of age and age-matched vehicle control	48
Rapamycin	4, 13, 20–22	Comprehensive organismal assessment (>25 tissues)	3–6 months of age and age-matched vehicle control	49
Metformin	12	Serum biomarkers	Age-matched ad libitum and dietary restricted	41
Metformin	12	Physical performance	Age-matched ad libitum	41
Metformin	12	Liver, muscle and gene expression	Age-matched ad libitum and dietary restricted	41
Resveratrol	12	Physiological metrics and gene expression	Age-matched untreated controls	54
Resveratrol	18	Renal function and histology	Age-matched untreated control	53
Ablation of senescent cells
Ablation of p16-positive cells	18	Adipose tissue metrics	Age-matched wild-type treated	88
Ablation of p16-positive cells	12	Kidney, heart and adipocyte metrics and function	12 months of age and age-matched vehicle control	62
Ablation of p16-positive cells	24	Vasculature function	Age-matched vehicle control	82
Ablation of p16-positive cells	12	Cartilage degeneration	Age-matched vehicle control	67
Ablation of p16-positive cells	24	Fat accumulation in liver	Age-matched vehicle control	64
Ablation of p16-positive cells	12, 20	Bone metrics and loss	Age-matched vehicle control	69
Ablation of p16-positive cells	>25	Renal function	Age-matched vehicle control	61
Dasatinib + quercetin	24	Cardiac metrics and function	Age-matched vehicle control	68
Dasatinib + quercetin	24	Vasculature function	Age-matched vehicle control	82
Dasatinib + quercetin	24	Fat accumulation in the liver	Age-matched vehicle control	64
Dasatinib + quercetin	20	Bone metrics and loss	Age-matched vehicle control	69
Dasatinib + quercetin	20	Physical performance	Age-matched vehicle control	70
ABT263	21–22	Immune system (HSC) and muscle (MuSC) function	2 months of age and age-matched vehicle control	65
UBX0101	2–3, 19–20	Cartilage regeneration	Age-matched vehicle control	67
FOXO4-DRI	24	Renal function and frailty	Age-matched vehicle control	61
Cellular reprogramming
Transient reprogramming	12	Pancreas regeneration	Age-matched vehicle control	105
Transient reprogramming	12	Muscle regeneration	Age-matched vehicle control	105

An extended version of this table with more details regarding the method of administration or procedure, duration of intervention, mouse strain and sex is available as Supplementary Table 1 HSC, haematopoietic stem cell; MuSC, muscle stem cell.